esfandiar heidarian

This study investigated the effects of gonadal removal in male and female rats on changes in serum biochemical parameters.

Twenty-eight adult male and female rats were divided into four groups of 7 animals for a period of 9 weeks. The first and second groups of intact male and female rats, as well as the third and fourth groups of male and female rats, were gonadectomized, respectively. At the end of the ninth week of the study, the rats were anesthetized with chloroform, and the amount of glucose, some lipid parameters in serum, and the activity of a number of serum enzymes were measured after taking blood from the heart.

Alanine aminotransferase, and alkaline phosphatase (ALP) levels were higher in intact male rats than in intact female rats, respectively (P=0.03, P=0.015). The amounts of glucose and cholesterol of low-density lipoprotein (LDL) in intact female rats were higher than in the ovariectomized rats, respectively (P=0.07, P=0.039, P=0.03). The amount of lactate dehydrogenase (LDH) in spayed female rats demonstrated a significant increase compared to other groups (P=0.001). However, there was a significant decrease in calcium levels in gonadectomized rat groups in comparison to intact female rats (P=0.02). Finally, a significant increase was found in phosphorous levels in the intact male rats group compared to other groups (P=0.002).

Decreased sex hormones in gonadectomized rats compared with intact rats could lead to increased serum levels of LDH, ALP, and LDL cholesterol that may result in the development of metabolic and atherogenesis syndromes and acute liver failure.

Hirudotherapy is very common in traditional Iranian medicine for treating various diseases, including hyperglycemia. However, there is no scientific research to evaluate its effect on diabetes mellitus and the possible side effects.

This study aimed to evaluate the biochemical and histopathological changes in healthy and diabetic male rats treated with leeches.

This experimental study was performed on 28 male Albino Wistar rats randomly divided into control, diabetic, and two treatment groups (control and diabetic rats treated with Hirudo medicinalis). Hirudotherapy was done in 3 to 5 minutes every 5 days for 28 consecutive days. At the end of the study, blood glucose, biochemical activity of the liver, kidney, and serum lipid enzymes were evaluated by enzymatic methods. Pathological changes in liver, kidney, and pancreas tissues were studied in the experimental groups.

The levels of blood glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatinine (Cr), urea, and phosphorus significantly increased in diabetic rats treated with leeches compared to the control group (P <0.05). In addition, liver tissue changes, such as hyperemia, degeneration, inflammatory cell infiltration, andfibrous tissue formation in the portal area, were observed in diabetic rats treated with leeches. Furthermore, renal tissue changes, including renal tubular degeneration and infiltration of inflammatory cells between renal tubules, were also observed in these rats.

Leech therapy is not beneficial for alloxan-induced diabetic rats and furthermaycause hepatotoxicity and acute renal failure.

Azathioprine (AZA) is an immunosuppressant medication that has toxicity to kidneys and liver. This study aimed to investigate the protective activity of carvacrol (CAR) against hepatorenal toxic activity of AZA in male Wistar rats.

All study rats were divided into five groups: control (saline, ip); azathioprine-only (AZA 50 mg/kg, ip), Sily+AZA (Silymarin 50 mg/kg, gavage), CAR+AZA (CAR 10 mg/kg, gavage), and CAR+AZA (CAR 20 mg/kg, gavage) groups. Silymarin was used as the standard hepatoprotective drug. The drugs were administered once daily for 21 days in III-V groups, and a single dose of AZA was injected on the seventh day of the experiment.

AZA-intoxicated rats exhibited an elevation in aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) activity in serum, as well as an increase in extent of lipid peroxidation. Activities of enzymatic antioxidants (superoxide dismutase – SOD, catalase - CAT) in the serum, liver, and kidney were decreased as for the AZA group (P < 0.05). Co-treatment of CAR (both doses of 10 and 20 mg/kg) lowered the serum transaminases and ALP level, the elevation of endogenous enzymes levels, and the malondialdehyde (MDA) in serum and both tissues (P < 0.05). This protective effect was greater in CAR 10 compared to 20 mg/kg doses, which was comparable to silymarin.

This study demonstrated that the renal and nephrotoxic activities of AZA could be attributed to the generated increased oxidative stress, as well as to the CAR with antioxidant effect similar to that in silymarin, which protected these tissues against AZA-induced nephrotoxicity hepatotoxicity.

This study investigated the effects of hydro-alcoholic extract of licorice root on the healing of surgical gastric ulcers in rats. For this experimental study, thirty-six male Wistar albino rats were prepared, and first, a 16 mm incision was made in the greater curvature of the stomach, and then it was sutured in a single layer. The rats were then randomly distributed into three groups (n=12), a control group, and two other groups, which were treated with licorice hydroalcoholic extract at doses of 150 and 300 mg/kg orally via gavage once daily for 21 consecutive days. Wound healing among the groups was compared and a determination was made for the malondialdehyde (MDA) concentration and serum antioxidant capacity. The mean rank of histopathological evaluation on the twentieth day after surgery showed a significant difference between the three groups. The difference in mean rank showed a significant increase between the group of rats treated with the extract at a dose of 300 mg/kg compared to the control group. The amount of MDA in the control group showed a significant increase compared to the groups treated with the extract at doses of 150 and 300 mg/kg. Serum antioxidant capacity in the experimental group treated with extracts showed a significant increase in comparison with the control group. The results of this study showed that lipid peroxidation in a gastrotomy rat treated with licorice root hydroalcoholic extract decreased with a marked increase in antioxidant activity and subsequently accelerated the healing process of the gastric surgery site.

As a herbicide, paraquat is a toxic agent that has devastating effects on human health. Gallic acid, on the other hand, is a natural compound that its anti-oxidant values have been reported in previous studies. Given these, this study was designed to evaluate whether gallic acid could reduce the toxic effects of paraquat in the liver of rats.

Six groups of rats were considered in this study. Group 1 (control group), group 2 (25 mg/kg of paraquat), group 3 (paraquat-plus-silymarin), and groups 4, 5, and 6 (paraquat together with gallic acid at the doses of 25, 50, and 100 mg/kg, respectively). After treatment, biochemical, oxidative, and histopathological parameters were evaluated in the rats.

We found that as compared to the control group, while paraquat reduced the hepatic levels of anti-oxidative compounds such as vitamin C (p<0.001), superoxide dismutase (SOD) (p<0.001), and catalase (CAT) (p<0.001), the toxic agent increased the serum levels of protein carbonyl (PC) (p<0.001), malondialdehyde (MDA) (p<0.05), and IL-1β (p<0.001). Paraquat also increased (p<0.05) both serum lipid profile and liver-associated markers in the rats. Nevertheless, gallic acid not only enhanced (p<0.05) the activity of vitamin C, SOD, and CAT but also remarkably reduced (p<0.05) the serum lipid profile, as well as the oxidative and inflammatory markers in the paraquat-treated rats. Gallic acid had also ameliorating effects on the damaged morphology of hepatocytes upon paraquat treatment.

The results of this study suggested that gallic acid possesses reinforcing effects on the antioxidant defense system and could be administered to reduce the toxicity of paraquat.

Docetaxel is widely used in the treatment of metastatic breast cancer. However, its effectiveness is limited due to chemoresistance and its undesirable side effects. The combination of chemotherapeutic agents and natural compounds is an effective strategy to overcome drug resistance and the ensuing inevitable toxicities. Quercetin is a natural flavonoid with strong antioxidant and anticancer activities. This study aimed to evaluate the cytotoxic and modulatory effects of combined docetaxel and quercetin on the MDA-MB-231 human breast cancer cell line. The cell viability was assessed by MTT assay. The induction of apoptosis was examined using flow cytometry. The role of p53 in the apoptotic process was evaluated via qRT-PCR. The levels of BAX, BCL2, ERK1/2, AKT, and STAT3 proteins were measured by Western blot analysis. The results showed that the single-agent treatment with docetaxel or quercetin leads to a decrease in the viability of the MDA-MB-231 cells at 48 h. Furthermore, the combination of docetaxel (7 nM) and quercetin (95 μM) displayed the greatest synergistic effects with a combination index value of 0.76 accompanied by up regulation of p53 and a significant increase in BAX level, as well as decreases in the levels of BCL2, pERK1/2, AKT, and STAT3 proteins (P < 0.05). The concomitant use of docetaxel and quercetin leads to the cell growth inhibition associated with the induction of apoptosis and inhibition of cell survival. Therefore, this study provides a promising therapeutic approach to enhance the efficacy of docetaxel in a less-toxic manner.

Bromelain enhances anticancer impacts to chemotherapeutic agents. The question as to whether bromelain does promote in-vitro cytotoxic and proapoptotic effects of cisplatin on human prostatic carcinoma PC3 cell line was investigated.

PC3 (human prostatic carcinoma) cells were treated either single or in combination with bromelain and/or cisplatin. MTT, clonogenic assay, flow cytometry and real-time quantitative polymerase chain reaction were used to investigate cell viability, colony formation, proapoptotic potential and p53 gene expression, respectively.

Cisplatin (IC10) combined with bromelain (IC40) significantly affected PC3 cell viability, inhibited colony formation, as well increased p53 proapoptotic gene expression compared to cisplatin single treatment. Nevertheless, bromelain-cisplatin chemoherbal combination did not display any additive proapoptotic effect compared to single treatments.

Bromelain-cisplatin chemoherbal combination demonstrated synergistic in-vitro anticancer effect on human prostatic carcinoma cell line, PC3, that drastically reduced required cisplatin dose. 

One of the most effective parameters in the progression of the prostate cancer is interleukin (IL)‑6 through affecting pSTAT3, pERK1/2, and pAKT cell signaling proteins. Carvacrol is an herbal antioxidant with antitumor effects. The purpose of this study was to investigate the effects of carvacrol on IL‑6 gene expression, pSTAT3, pAKT, pERK1/2 cellular signaling proteins, and invasion in human prostate cancer PC3 cells.

PC3 cell viability was evaluated by MTT assay with different concentrations of carvacrol (0–800 µM). IL‑6 gene expression and cellular concentration of pSTAT3, pERK1/2, and pAKT were investigated using the real‑time reverse transcription quantitative polymerase chain reaction (RT‑qPCR) and western blotting technic, respectively. PC3 cell invasion was determined by invasion assay test.

Carvacrol IC 50 for PC3 prostate cancer cells was 360 µM. Carvacrol led to a significant reduction (P < 0.05) for IL‑6 gene expression in a dose‑dependent manner compared to control. IL‑6 protein reduced 41.5% and 52.7% when compared with control cells at 360 and 420 µM of carvacrol, respectively.Carvacrol led to a decline in pSTAT3, pAKT, and pERK1/2 above 360 µM compared to control. PC3 potential invasion was significantly reduced after treatment with carvacrol in a dose‑dependent manner.

Decreased IL‑6 protein level by carvacrol resulted in diminishing of pSTAT3, pERK1/2, and pAKT signaling proteins, which leads to the reduction of the cell survival, proliferation, and invasion in PC3 cells.

Bromelain is dotted with anticancer properties on various cancer cell lines. Anticancer pathways of bromelain, as well related intervening signalization are under investigation. Investigating the inhibitory potential of bromelain on AGS, PC3, and MCF7 cells proliferation and colony formation. The bromelain inhibitory potential on AGS, PC3, and MCF7 cells proliferation at various bromelain concentrations was assessed by MTT; thereby, bromelain potency on colony formation impediment was evaluated using clonogenic assays at determined 50% inhibitory concentrations (IC50) on four different cell densities (10, 50, 100, and 200 cells per well). Bromelain inhibits AGS, PC3, and MCF7 cells proliferation in such a dose‑dependent manner. Determined IC50 to AGS, PC3, and MCF7 cells were 65, 60 and 65µg/ml respectively. At IC50, bromelain significantly suppressed the AGS, PC3, and MCF7 cells colony formation at four treated densities (10, 50, 100 and 200 cells per well). Plating efficiency percentage and cell surviving fraction were decreased after bromelain treatment to AGS, PC3, and MCF7 human cancer cells as a function of initial cell density. The 50, 50 or 100, and 10 or 50 cells per well were considered to be optimum number of initial cell density for AGS, PC3, and MCF7 cells. Cell proliferative and colony formation inhibition are two pathways to in vitro bromelain anticancer effects. The current study displayed a dose‑dependent inhibitory effect of bromelain, as well impeding colony formation AGS, PC3, and MCF7 human cancer cells.

Paraquat is a herbicide with potent toxicity in humans and animals. This study aimed to evaluate the protective effects of Origanum vulgare (O. vulgare) leaf extract on the acute nephrotoxicity and renal oxidative stress caused by paraquat.

We randomly assigned forty male rats into five groups (G1-G5). The G1 was used as control; G2 only received paraquat (25 mg/kg body weight (bw)/day, po); and G3, G4 and G5 received 25 mg/kg b.w/day oral doses of paraquat and O. vulgare hydroethanolic leaf extract (200, 400, 800 mg/kg bw/day, po, respectively). After 2 weeks, superoxide dismutase (SOD), renal catalase (CAT), vitamin C levels, histopathological changes, and tumor necrosis factor-α (TNF-α) gene expression as well as serum levels of urea, creatinine (Cr), and protein carbonyl (PC) were determined.

In G2, oral administration of paraquat significantly increased (p<0.05) serum Cr, urea, PC, and renal TNF-α gene expression relative to those of the control group. Renal catalase, superoxide dismutase, and vitamin C levels were decreased significantly (p<0.05) in G2 as compared to G1. Administration of O. vulgare leaf extract not only increased the renal vitamin C, CAT, and SOD but also decreased the renal TNF-α gene expression, malondialdehyde (MDA), serum urea and creatinine in paraquat-induced nephrotoxicity in rats.

Our results show that O. vulgareleaf extract has protective effects against nephrotoxicity induced by paraquat in rats. It seems that the nephroprotective effects of O. vulgare extract may be related to its antioxidant and anti-inflammatory effects.

One of the most common malignancies in women is breast cancer. B-escin has pharmacological anticancer effects. 5-fluorouracil (5-FU) has antimetabolite and antiproliferative properties. The purpose of this study was to investigate the combined effects of 5-FU and B-escin on apoptosis, colony formation, Bcl-2 signaling protein, and p53 gene expression in MCF7 breast cancer cell line. The cytotoxic effects, the number of colonies, apoptosis, p53 gene expression, and Bcl-2 signaling protein of the combined 5-FU and B-escin on MCF7 cells were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, clonogenic assay, flow cytometry, real-time quantitative polymerase chain reaction, and western blotting methods, respectively. Half-maximal inhibitory concentration values of B-escin and 5-FU were 80 Micro g/ml and 2 Micro M, respectively. The combination of 5-FU and B-escin on MCF7 cell viability showed a combination index equal to 0.5. The expression of p53 and apoptosis increased in the combination of 5-FU and B-escin on MCF7 cells compared to that of control group (P < 0.05). In addition, the number of colonies and Bcl-2 signaling protein in combination of 5-FU and B-escin decreased with respect to untreated control cells or single treatment of 5-FU and B-escin. The combination of 5-FU and B-escin not only has synergistic effects by increasing cell apoptosis and p53 gene expression but also decreases Bcl-2 signaling protein in MCF7 cell lines.

Prostate cancer is as far the most prevalent male cancer. Rutin (a glycoside fromquercetin flavonoid) displays antioxidant activity leading to cell apoptosis. Combined effects ofrutin with the widely used anti-cancer drug, 5-fluorouracil (5-FU), on prostate cancer cell line(PC3) was investigated herein. Different concentrations of combined 5-FU and rutin were applied to PC3 cellscompared to separate treatment for 48 hours. Cell viability, as well p53 gene expressionrespectively were assessed by MTT assay and real-time quantitative polymerase chain reaction(qPCR). Changes of Bcl-2 signal protein and apoptosis were determined using western blotand flow cytometry procedures, respectively. Clonogenic assay was used to colony countsassessment. 50% inhibitory concentration (IC50) of separate cell treatment with either rutin and5-FU respectively were 900 μM and 3Mm, while combination index (CI) of combined 5-FU/rutin application reached a level of synergistic effects (0.33). Combination of 5-FU/rutinenhanced apoptosis and p53 gene expression in PC3 cells. PC3 cell colony counts and Bcl-2signaling protein were decreased by 5-FU/rutin combination. Synergistic effects of 5-FU/rutin combination on PC3 cells line enhanced apoptosis,p53 gene expression, and down-regulation of Bcl-2 protein, compared to control separateapplication. 5-FU/rutin combination does seem an interesting therapeutic pathway to be furtherinvestigated.

Since active plant ingredients can induce apoptosis in many tumors, in this studywe evaluate the apoptotic effects of thymoquinone (TQ) on PC3 cells. Also, we predicted theinteraction of TQ with BCL-XL, BCL-2, and MCL-1anti-apoptotic factors by computer-simulatedenvironment. PC3 cells were treated with different concentrations of TQ (0- 80 μM) and IC50 wasdetermined using 3-(4, 5-dimethylthiaztol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay.Apoptotic and cytotoxicity effects of TQ were analyzed using flowcytometry and comet assay,respectively. Changes in energy and the molecular interactions of TQ with BCL-XL, BCL-2 andMCL-1 anti-apoptotic factors were investigated using simulation. IC50 value was 40 μM. TQ led to the destruction of the genome of PC3 cells and inducingapoptosis. Molecular dynamics (MD) revealed that the root mean-square deviation (RMSD),root mean square fluctuation (RMSF), radius of gyration (Rg), and the number of hydrogen andhydrophobic bonds between TQ and residues of BCL-2, BCL-XL and MCL-1were significantly(P < 0.001) changed. TQ makes a more stable and stronger connection with BCL-XL comparedto BCL-2 and MCL-1 and inhibits BCL-XL non-competitively. Our results demonstrated that TQ not only led to apoptosis, at least partly, due toreduction in the Coil, Turn, and Bend structure of BCL-XL but also caused a decrease in the Rgand RMSD value of BCL-XL, MCL-1, and BCL-2.

Diclofenac (DIC) is one of the compounds derived from acetic acid which isknown for its anti-inflammatory and analgesic attributes. Silymarin is a flavonoid compoundwhich is derivate from Silybum marianum seeds. This research was done to assess the protectiverole of silymarin against liver toxicity induced by DIC in male rats. Randomly, 40 male Wistar rats were assigned into five groups as follows: Group 1:control group, Group 2: DIC-only treated (50 mg/kg, i.p), Group 3: silymarin-only treated (200mg/kg, p.o); Groups 4 and 5: DIC (50 mg/kg, i.p) plus silymarin (100 mg/kg and 200 mg/kg, p.o,respectively) treated. Various biochemical, molecular, and histological parameters were evaluatedin serum and tissue. In the DIC-only treated group, the levels of liver glutathione peroxidase (GPx), superoxidedismutase (SOD), intracellular glutathione (GSH) and catalase (CAT) significantly diminished andthe levels of total bilirubin, alkaline phosphatase (ALP), nitrite, alanine aminotransferase (ALT),malondialdehyde (MDA), serum tumor necrosis factor-α (TNF-α), aspartate aminotransferase(AST), and TNF-α gene expression were remarkably elevated relative to control animals. In otherhands, treatment with silymarin caused a noticeable elevation in GPx, SOD, GSH, CAT and aremarkable reduction in levels of total bilirubin, ALP, nitrite content, ALT, MDA, serum TNF-α,AST and TNF-α gene expression relative to DIC-only treated group. Histopathological injurieswere also improved by silymarin administration. The results confirm that silymarin has an ameliorative effect on liver toxicity inducedby DIC and oxidative stress in male rats.

The significant contribution of nanoparticles to cancer treatment has attracted therapeutic attention. The present study aimed to evaluate the synergistic effects of 5-fluorouracil (5-FU) and zinc oxide nanoparticles (ZnO NPs) as multimodal drug delivery on human breast cancer MCF-7 cells. In this in-vitro study, the impact of 5-FU and ZnO NPs in the single or combined forms was evaluated on cell viability, colony formation, apoptosis, p53 gene expression, and Bcl-2 signaling protein in MCF-7 breast cancer cell line using several techniques, such as MTT, clonogenic assay, flow cytometry, real-time quantitative polymerase chain reaction, and Western blot. In this study, 5-FU combined with ZnO NPs showed synergistic effects against MCF-7 within 48 hours. In addition, the combination of 5-FU and ZnO NPs at the respective concentrations of 1 µM and 45 µg/ml exhibited significant apoptosis (79.53%), p53 gene expression (3.6 folds), reduction of cell invasion (9.82%), and plating efficiency (5%), thereby leading to the significant reduction of cell viability (40±0.9%) and decreased Bcl-2 anti-apoptotic protein relative to untreated control cells. According to the results, the synergistic effects of combined ZnO NPs and 5-FU on MCF-7 human breast cancer cells were exerted via Bcl-2 inhibition and the up-regulation of p53 expression.

Diclofenac (DIC), a phenylacetic acid compound which belongs to nonsteroidal anti-inflammatory drugs (NSAIDs), is generally used for the treatment of various diseases such as rheumatoid arthritis, ankylosing spondylitis, acute muscle pain conditions and osteoarthritis. Overdose of DIC can lead to renal injuries in both experimental animal and human. Our research was done to assess the protective role of silymarin on renal damage induced by DIC in rats. Thirty-two Wistar rats were assigned to four groups (n=8/group). Group 1 was control group; animals in group 2 were administrated DIC; Groups 3 and 4 administrated DIC plus silymarin with doses of 100 mg/kg and 200 mg/kg, orally (p.o), respectively. Various biochemical, molecular, and histological parameters were evaluated in serum and tissue homogenate. In the second group, the levels of kidney catalase (CAT), vitamin C and superoxide dismutase (SOD) remarkably reduced (P < 0.05) relative to the control group. Also, urea, creatinine (Cr), malondialdehyde (MDA), serum tumor necrosis factor-α (TNF-α) and gene expression of TNF-α in this group were noticeably elevated (P < 0.05) relative to the control group. Treatment with silymarin caused a remarkable elevation (P < 0.05) in vitamin C, SOD, CAT and a remarkable reduction (P < 0.05) in the content of MDA, urea, Cr, TNF-α gene expression and serum TNF-α in comparison with second group. Histological injuries were also ameliorated by silymarin administration. The results confirm that silymarin has an ameliorative role against renal damage and oxidative stress induced by DIC in male rats.

Pioglitazone increases insulin sensitivity and improves glycemic control in type 2 diabetics. In this study, we evaluated the effects of pioglitazone on the uncoupling protein 1 (UCP1) expression in mouse brown adipose tissue (BAT), and on recovery from oxidative stress due to a high-fat diet. 30 mice were divided into three groups: group 1 received a normal diet, group 2 received a high-fat diet, and group 3 received a high-fat diet plus 30 mg/kg pioglitazone. After treatment, the cholesterol, triglyceride, paraoxonase 1 (PON1), total serum antioxidant capacity (TAC), malondialdehyde (MDA), and specific activity of hepatic catalase were measured. BAT UCP1 expression was evaluated at both the mRNA and protein levels. The weights differed between the groups (p<0.05). Serum MDA was greater and TAC, liver catalase, and PON1 were less than in group 2 than in group 1 (p<0.05). In Serum MDA was less and catalase activity was greater in group 3 than in group 2 (p<0.05). UCP1 gene expression was less in group 2 than in group 1 (p<0.05) but greater than in group 3 (p<0.05). Pioglitazone may have a protective role in high-fat-diet-induced oxidative stress by increasing the antioxidant capacity. Moreover, it can induce weight loss by increasing UCP1 mRNA and protein expression.

Breast cancer (BC) remains the leading cause of death in women worldwide, despite the improvements of cancer screening and treatment methods. Recently, development of novel anticancer drugs for the improved prevention and treatment of BC is in the center of research. The anticancer effects of bromelain, as enzyme extract derived from the pineapples, contains chemicals that interfere with the growth of tumor cells. The aim of this study was to evaluate the effect of radiosensitizing of bromelain in 4T1 BC cells. This investigation utilized the 3-(4,5-dimethylthiazol-2-yl)-2,5-dimethyltetrazolium bromide assay to characterize the cytotoxicity of bromelain. Colony formation assay used to confirm the ability of bromelain to sensitize BC cells to RT. Flowcytometry performed to define the contribution the apoptosis effect to bromelain mediated radiosensitization of 4T1 cells. Bromelain reduced growth and proliferation of 4T1 cell as a concentration-dependence manner significantly. The survival of 4T1 cancer cells was decreased after combined treatment in a number and size-dependent manner with respect to the control group (P < 0.05). Combination of bromelain with radiation does not influence 4T1 cell apoptosis. The results suggested that bromelain can inhibit the growth and proliferation and reduce survival of 4T1 BC cells and might be used as a candidate radiosensitizer in BC patient.

Paraquat is a quaternary nitrogen herbicide which induces kidney toxicitydue to producing oxidative stress. We have investigated the potential protective effects ofsilymarin on paraquat-induced renal toxicity. Twenty-four male rats were divided into three groups, group 1, control group;group 2, rats that received paraquat only (25 mg/kg b.w./day, po); animals in group 3, wastreated with paraquat (25 mg/kg b.w./day, po) and silymarin (50 mg/kg b.w./day, po). Then,the serum and tissue parameters of the oxidative stress and renal histopathological changeswere examined. In group 2 which received paraquat only, a remarkable increase (P<0.05) was observedin serum creatinine, urea, malondialdehyde (MDA), protein carbonyl, and tumor necrosisfactor alpha (TNF-α). Also, there was a significant decrease in renal superoxide dismutase,catalase (CAT), ferric reducing ability of plasma (FRAP) and vitamin C in the second group.Oral administration of silymarin significantly decreased serum urea, creatinine, proteincarbonyl, MDA, and TNF-α as well as renal histopathological changes. The present study suggests that silymarin has anti-inflammatory andnephroprotective effects against nephrotoxicity caused by paraquat.

In this study, the effects of Urtica dioica hydro-alcoholic extract were investigated on the blood glucose and lipid profiles of female ovariectomized and non-ovariectomized rats. In total, 32 adult female rats were divided into four groups (eight each) including control and ovariectomy groups as well as non-ovariectomy and ovariectomy groups treated with 200 mg kg-1 of Urtica dioica extract orally in the last five weeks of the study starting from the week 56th. The duration of the study was 60 weeks. Glucose, serum lipid profiles and pancreatic pathological alterations were determined in these groups at the end of experiment. Serum glucose, triglyceride (TG), very-low-density lipoprotein (VLDL), and TG/high-density lipoprotein (HDL) ratio indicated a significant increase in the healthy female rats under treatment with Urtica dioica extract compared to others. The TG, cholesterol, HDL, low-density lipoprotein (LDL) and VLDL showed a significant increase in menopaused rats compared to others. The interaction of consuming Urtica dioica extract and ovariectomy caused significant decreases in glucose, TG, VLDL, HDL/LDL ratio and TG/HDL ratio. Consumption of Urtica dioica extract by non-menopaused rats damaged the beta cells in Langerhans islets. Results of the present study revealed that the consumption of Urtica dioica extract is not beneficial and has diabetogenic effects in female non-ovariectomized rats compared to ovariectomized ones.

Uncoupling protein‑1 (UCP‑1) is the index protein of the brown adipose tissue (BAT), used in the obesity studies. We evaluated the effects of thymoquinone (TQ), hydroalcoholic, and hexane extracts of Nigella sativa, on the UCP‑1 gene expression in BAT, and also on the recovery from oxidative stress, due to a high‑fat diet.

Fifty mice were divided into five groups: the first group was fed with a usual diet and the second, third, fourth, and fifth groups with a high‑fat diet, hydroalcoholic extract, hexane extract, and TQ, respectively. After completing the course, the lipid profile, paraoxonase 1 (PON1), serum total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured. UCP‑1 expression in BAT was evaluated at the gene and protein level.

The weight of mice, receiving TQ, hydroalcoholic, and hexane extracts, was decreased (P < 0.05), compared to the second group (P < 0.05). MDA was increased in the second group, compared to the first group (P < 0.05); however, TAC, liver catalase enzyme, and PON1 were decreased (P < 0.05). Furthermore, MDA of the third, fourth, and fifth groups had decreased, and the activity of PON1, liver catalase enzyme, and the amount of TAC was increased (P < 0.05). UCP‑1 expression of the third and fourth groups was increased, compared to the second group (P < 0.05).

The results suggest that TQ, hydroalcoholic, and hexane extracts of N. sativa have a protective and therapeutic role in the oxidative stress, caused by high‑fat diets. The hydroalcoholic and hexane extracts can induce weight loss, by positively affecting UCP‑1, at the gene and protein level

MTT assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] is a sensitive and accurate method to determine survival fraction of irradiated cancer cells. The aim of present study was to evaluate the radiosensitivity of cancer cells X-ray Irradiation in comparison to normal cells using the MTT assay.
Four cancer cell lines were used, the mouse breast 4T1 cells, the mouse fibroblast L929 cells, the human gastric AGS cells, and the human dermal fibroblasts (HDF) cells. For each cell line, MTT assay was carried out after irradiation to 0, 2, 4, and 6 Gy. For MTT assay, the relationship between absorbed dose and cell number, optimal seeding of cell number, and optimal timing of assay were determined. Then, MTT assay was performed when the irradiated cells had regained exponential growth, or when the non-irradiated cells had undergone doubling times.
Findings: With increasing radiation dose, the mortality of the cells increased, and radiation blocked cell growth.
The response of different cells to irradiation was different. MTT assay may successfully be used, and also may distinguish cell responses to different photon energies. MTT assay was undertaken with optimal assay conditions, and showed the sensitivity of cells to irradiation with regard to the plating efficiency of each cell line, and doubling time at least.

Prostate cancer (PC) is a malignant disease, which is common in men. Interleukin‑6 (IL-6) mediates the progression of PC through PI3K/AKT, JAK-STAT, and ERK1/2 MAPKs signaling pathways. Gallic acid, a phenolic compound, has anti-oxidant, anti-proliferative, and anti‑tumorigenic properties.
This study was undertaken to evaluate the effects of gallic acid on DU-145 cell viability, proliferation, invasion, IL-6 gene expression, and the cellular levels of phosphorylated STAT3, ERK1/2, and AKT signaling proteins.
DU-145 cells were treated with gallic acid (0 - 100 µM). The 3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide (MTT) assay was done in order to evaluate the cytotoxicity of gallic acid on DU-145 cells. IL-6 gene expression was investigated, using RT-qPCR. The levels of phosphorylated ERK1/2, AKT, and STAT3 signaling pathways were assessed by Western blotting technic. DU-145 cells invasion were measured by invasion assay test.
A significant reduction was observed in viability, proliferation, and invasion of DU-145 cells after treatment with gallic acid. Also, cellular levels of phosphorylated STAT3, ERK1/2, and AKT signaling proteins decreased after 48 hours in a dose-dependent manner by gallic acid. Secretion and gene expression of IL-6 were decreased in DU-145 cells treated with gallic acid.
The results of this study showed that gallic acid can lead to a reduction in survival, proliferation, and invasion in DU-145 cell line by reducing protein IL-6 and its gene expression, pSTAT3, pERK1/2, and pAKT signaling protein pathways. Therefore, it seems that gallic acid can be regarded as a potent agent in the treatment of prostate cancer.

All natural anticancer agents are cytotoxic basically and act mainly by the inhibition cell proliferation; but they have different mechanisms. Two assays, thiazolyl blue [3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyl-terazoliumbromide or MTT] and sulforhodamine B (SRB), are used to assess cell growth. This study aimed to compare measurements between MTT and SRB on the cancer cell lines.
Different concentrations of the bromelain were added to cultured cells including mouse breast cancer (4T1), human gastric carcinoma (AGS), and human prostate carcinoma (PC3) cell lines and incubated at 24 and 48 hours. The growth and proliferation rates of the studied cells were investigated using both MTT and SRB assays after treatment with bromelain. The differences between cells were determined using Kruskal-Wallis and Dunns tests.
Findings: Bromelain significantly decreased growth and proliferation rate of 4T1, AGS and PC3 cancer cells, in a concentration-dependent manner at different times, in both MTT and SRB assays.
Findings showed that both MTT and SRB assays gained similar data regardless of the cell types.