The present study sought to evaluate the beneficial effects of histidine (His) on oxidative stress, tumor necrosis factor alpha (TNF-α), renal histological alterations and anti-oxidant enzymes gene expressions in type 2 diabetic rats. Streptozotocin/nicotinamide (STZ/NA) induced diabetic rats were used as an animal model of type 2 diabetes. One group of rats received daily His (1000 mg/l) in drinking water for 8 weeks, whereas other groups (control and untreated diabetic groups) received only water. Different parameters such as glucose, insulin, insulin resistance, lipid profile, cardiac risk ratios, renal functional markers, and oxidative stress were determined in all groups. Moreover, renal histological alterations, mRNA expressions of anti-oxidant enzymes, and TNF-α were evaluated in the rats. His exhibited a protective effect on glucose, insulin, insulin resistance, lipid profile, cardiac risk ratios, renal functional markers, oxidative stress, and TNF-α. Furthermore, His restored the renal histological alterations and normalized the augmented mRNA expressions of renal anti-oxidant enzymes (glutathione peroxidase (GPX) and Cu-Zn superoxide dismutase (Cu-Zn SOD)) and TNF-α. His could ameliorate diabetes complications related to oxidative stress, inflammation, dyslipidemia, hyperglycemia, insulin resistance, and nephropathy. Hence, the use of this amino acid is recommended for diabetic patients in order to reduce diabetes complications.

Iron is an essential element for living organisms. Iron overload can have detrimental effects on health. This study pertains to the protective role of berberine against ferrous sulfate-induced hepatic and renal functional disorders and histological damages in rats.
The rats were divided into four groups (n=7): Sham, Ber (10 mg/kg/day for 14 days, by gavage), FS (ferrous sulfate, 30 mg/kg/day for 14 days, intraperitoneally), FS Ber (ferrous sulfate, 30 mg/kg/day for 14 days; berberine, 10 mg/kg/day for 11 days from fourth day of ferrous sulfate injection). After 24 hr, blood, urine, and tissue samples were collected.
Compared with sham and Ber groups, administration of ferrous sulfate resulted in liver and kidney dysfunction as evidenced by significantly higher levels of serum hepatic markers and bilirubin, and lower levels of serum albumin, total protein, triglyceride, cholesterol, and glucose, as well as lower creatinine clearance and higher fractional excretion of sodium. This was accompanied by increased malondialdehyde levels and histological damages. Berberine treatment significantly reversed the levels of serum hepatic markers, renal functional markers and lipid peroxidation marker in the FS Ber group. Furthermore, it restored the levels of serum total protein, albumin, glucose, triglycerides, and cholesterol with a decrease in bilirubin concentration in the blood. All these changes were corroborated by histological observations of the liver and kidney.
Berberine protects the liver and kidneys against ferrous sulfate-induced toxicity by reduction in lipid peroxidation and ability to chelate iron.

Nitrofurantoin (NFR) is an antibiotic commonly used in the management of uncomplicated urinary tract infections. The study examined histoarchitectural and biochemical alterations in the liver and kidney of Wistar rats following exposure to nitrofurantoin. Fifteen (15) adult Wistar rats comprising five (5) animals per group were randomly assigned into three groups. Group A was the control group while Groups B and C received 30mg kg-1 and 60mg kg-1 body weight of NFR respectively for thirty (30) days. Data generated from liver and renal functional markers was analyzed on graph pad prism using descriptive statistics and outcomes implicated as standard error of the mean and mean. Mean value differences were evaluated using analysis of variance (ANOVA) considering p<0.05 as statistically significant value. Upshot display periportal hepatitis in the group given 30mg kg-1 of nitrofurantoin, the hepatocytes appeared polygonal and there was vascular congestion with inflammatory cell infiltration in rats given 60mg kg-1 NFR. These features were consistent with inflammatory responses. However, liver function tests showed a significant increase in Alanine transaminase (ALT), Aspartate aminotransferase (AST), and Alkaline phosphatase (ALP) levels across treated groups when rationalized to control group (p<0.05). Also observed is a statistically significant increase in mean serum level of total protein, direct and indirect Bilirubin across treatment groups compared to control. More so, there were features consistent with normal renal histoarchitecture with tubules comprising of multiple segments and corpuscle made up of the Glomerulus surrounded by the podocytes. Conversely, renal function parameters showed a decrease in the urea level across treatment groups. Nitrofurantoin displays no histoarchitectural outcome of the kidney but elucidated negative outcome on the liver histology, therefore caution should be considered when administered as a therapeutic agent.

Renal ischemia-reperfusion injury (RIR) occurs when there is a temporary restriction of blood flow to the kidneys followed by an influx of blood, re-oxygenating the tissues. This occurs as a severe complication of major surgery. This process causes significant damage to the tissues and is responsible for the development of acute kidney injury (AKI), a life-threatening condition with high mortality rates. Here, we evaluated the potential protective effects of the antioxidant, gallic acid (GA), on RIR in an in vivo rat model. Adult male Sprague Dawley rats were randomly divided into three groups: group 1 (control, n = 8), group 2 (Ischemia-reperfusion (IR) with no-treatment, n = 7), and group 3 (IR + daily GA 100 mg/kg i.p, n = 7). The abdomens of the rats in the control group were opened during the surgical procedure, then sutured closed. GA pretreatment began daily 15 days prior to inducing RIR. To induce RIR, the umbilical arteries were obstructed on both sides and clamped with mild pressure for 45 min. Following the 45 min ischemia, the clamps were removed to allow for the induction of reperfusion. The reperfusion phase was 24 hours. Following IR, the serum levels of urea and creatinine significantly increased compared to the controls. Pretreatment with GA was observed to reduce urea and creatinine levels following IR. However, this decrease was not statistically significant. The serum and renal levels of malondialdehyde (MDA) in the IR group was significantly elevated compared to the control group. Conversely, glutathione (GSH) levels and the activity of glutathione peroxidase (GPX) significantly decreased in the IR group compared to controls. Our findings show GA pretreatment to significantly improve the levels of renal MDA, serum GSH, and GPX activity following RIR. Our findings highlight the protective role for GA in mitigating the damage caused by RIR and its applications as a potential treatment.

Several studies indicate that gender differences exist in tolerance of the kidney to ischemia reperfusion (IR) injury. Recently، postconditioning (POC)، induction of brief repetitive periods of IR، has been introduced to reduce the extent of the damage to the kidney. This method was shown to attenuate renal IR injury by modifying oxidative stress and reducing lipid peroxidation. Considering the gender effect on the results of several treatment methods، in this study، we investigated the impact of gender on the protective effect of POC on the rat kidney. In this study، after right nephrectomy، 48 male and female rats were randomly divided into 6 groups of 8 rats: In IR group، with the use of bulldog clamp، 45 minutes of left renal artery ischemia was induced followed by 24 hours of reperfusion. In the sham group، all of the above surgical procedures were applied except that IR was not induced. In the POC group، after the induction of 45 minutes ischemia، 4 cycles of 10 seconds of intermittent ischemia and reperfusion were applied before restoring of blood to the kidney. 24 hours later، serum and renal tissue samples were collected for renal functional monitoring and oxidative stress evaluation. Postconditioning attenuated renal dysfunction considering the significant decrease in plasma creatinine and BUN compared with IR group only in male rats (P<0. 05). Also، POC attenuated oxidative stress in male rats’ kidney tissues as demonstrated by a significantly reduced malondialdehyde (MDA) level and increased superoxide dismutase (SOD) activity (P<0. 05). In female rats، there were no changes in functional markers and oxidative stress status in POC group compared to IR group. Considering gender difference، POC had protective effect against IR injury by attenuating functional and oxidative stress markers in male rat kidneys. This protective effect was not seen in female rats.

The present study aimed to investigate the role of adenylyl cyclase activator in preventing diabetic nephropathy via antioxidant activity in rats. Biochemical parameters were performed to confirm Streptozotocin induced nephropathy in rats. Male Wistar rats were used in the present study to reduce the effect of estrogen. Rats were subjected to high fat diet (HFD) for two weeks followed by low dose of Streptozotocin (STZ) [35mg/kg, i.p.] to develop experimental diabetic nephropathy in eight weeks. Two weeks treatment with low dose of Forskolin (10mg/kg) reduced the level of diabetic nephropathy markers but results observed were not significant. Whereas, Forskolin intermediate dose (20mg/kg) and high dose (30mg/kg) treated rats significantly attenuated diabetes induced elevated renal function parameters and endogenous antioxidants enzymatic activities. High dose of Forskolin was found to be more effective in attenuating the renal structural and functional abnormalities. Forskolin prevented renal structural and functional abnormalities diabetic rats. In the present study, Glibenclamide (0.6mg/kg) and Atorvastatin (0.5mg/kg) were used as standard drugs. Our results demonstrated synergistic effects, when high dose of Forskolin was co-administered with standard drugs. In conclusion, treatment with adenylyl cyclase activator, Forskolin in diabetic rats reduced the oxidative stress, improved renal functions and enhanced level of endogenous antioxidants. Forskolin prevented renal functional abnormalities due to diabetes mellitus. Forskolin has a potential to prevent diabetic nephropathy, implicating direct renoprotective action in diabetic rats.

The aim of this study was to investigate the effect of angiotensin II (Ang II) and losartan injections into paraventricular nucleus (PVN) on renal ischemia-reperfusion injury. After right nephrectomy in male rats, a cannula was inserted into the right PVN. One week later, renal ischemia-reperfusion (IR) injury was induced by clamping the left renal artery for 45 min, and then the kidney was reperfused for 24 h. An Ang II AT1 receptor antagonist, losartan (0.3 μg) was injected into the PVN 20 minutes before the induction of ischemia, followed by 3 ng of Ang II after 10 minutes. Blood, urine and kidney samples in addition to the brain area containing the PVN were collected to evaluate different indices. Renal sympathetic nerve activity (RSNA) was recorded in all groups. Angiotensin II injection into PVN caused significant increases in renal functional (plasma creatinine and BUN as well as urinary NAG activity) and histological indices in comparison to IR group (p<0.05). Losartan injection before Ang II into PVN significantly reduced these markers (p<0.05). In addition, angiotensin II caused significant increases in oxidative stress in PVN (higher MDA and lower SOD) and RSNA compared to the IR group (p<0.05). Losartan improved these markers significantly (p<0.05). This study showed that Ang II injection into PVN increases oxidative stress in PVN and renal sympathetic nerve activity through AT1 receptors and exaggerates renal ischemia-reperfusion injury.

Iron overload in the body is related with toxic effects and threatens the health. The aim of this study was to evaluate the protective role of hydroalcoholic extract of ginger (Zingiber officinale) against ferrous sulfate-induced hepatic and renal functional disorders and histological damages in rats.
The rats were divided into four groups (n=7): Sham, Sham G.E (ginger extract, 400 mg/kg/day for 14 days), FS (ferrous sulfate, 30 mg/kg/day for 14 days), FS.E (ferrous sulfate, 30 mg/kg/day for 14 days; ginger extract, 400 mg/kg/day for 11 days from the fourth day of ferrous sulfate injection). After 24 hr, blood, urine and tissue samples were collected.
Compared with Sham and Sham G.E groups, administration of ferrous sulfate resulted in liver and kidney dysfunction as evidenced by significantly higher levels of serum hepatic markers and bilirubin, and lower levels of serum albumin, total protein, triglyceride, cholesterol and glucose, as well as lower creatinine clearance and higher fractional excretion of sodium (p In conclusion, ginger extract appears to exert protective effects against ferrous sulfate-induced hepatic and renal toxicity by reducing lipid peroxidation and chelating iron.

Induction of septic shock by lipopolysaccharide (LPS) may lead to acute renal failure. The present study aimed to investigate the impact of sex differences on the effectiveness of low-dose LPS preconditioning (LPS-PC) on LPS-induced acute renal failure in rats. This study was conducted at Tehran University of Medical Sciences, in 2017. A total of 48 Wistar rats were equally divided into two groups of male and female rats. The rats in each group were then allocated to three groups (n=8 per group), namely control, septic shock, and LPS-PC group. A high dose of LPS was administered for septic shock induction. LPS-PC was induced by injecting LPS before sepsis induction. The effect of sex differences on renal functional indices, renal oxidative stress markers, plasma tumor necrosis factor-α level, and renal histological changes was evaluated. Data were analyzed using two-way ANOVA followed by Tukey’s post hoc test. In the septic shock groups, renal functional parameters (creatinine [Cr] and blood urea nitrogen [BUN]) were increased in both sexes. However, the increase was more significant in male rats (male rats: Cr=2.14±0.13, BUN=81±4.15; female rats: Cr=1.64±0.12, BUN=50±2.7). LPS-PC reduced these indices in both sexes (male rats: Cr=1.24±0.03, BUN=57±4.1; female rats: Cr=0.86±0.02, BUN=30.31±2.25). Renal superoxide dismutase (SOD) activity (male rats: 11.54±1.34, female rats: 24.4±2.04) and catalase (CAT) activity (male rats: 15±1.74, female rats: 25.75±1.97) were significantly higher in the female septic group. LPS-PC significantly increased SOD (male rats: 25.7±2.45, female rats: 42.6±3.31) and CAT (male rats: 37.25±2.34, female rats: 59.21±3.29) activities in renal tissue samples in the LPS-PC group in both sexes compared to the septic groups. In the LPS groups, plasma tumor necrosis factor-α (male rats: 375±25.65, female rats: 285.45±25.94) were significantly higher than in the LPS-PC groups (male rats: 250±21.35, female rats: 121±24.14). Male rats were more susceptible to sepsis-induced renal damage. LPS-PC had protective effects on the LPS-induced renal injury, and these effects were most prominent in female rats.

Hyperglycemia mediated oxidative stress plays a key role in the pathogenesis of diabetic complications like nephropathy. In the present study, we evaluated the effect of ethanolic extract of Ensete superbum seeds (ESSE) on renal dysfunction and oxidative stress in streptozotocin-induced diabetic rats. Glucose, HbA1c, total protein, albumin, renal function markers (urea, uric acid and creatinine), and lipid peroxidation levels were evaluated. Renal enzymatic and non-enzymatic antioxidants were examined along with renal histopathological study. ESSE (400 mg/kg BW t) administration reduced glucose and HbA1c, and improved serum total protein and albumin in diabetic rats. ESSE in diabetic rats recorded decrement in renal function markers and renal lipid peroxidation products along with significant increment in enzymatic and non-enzymatic antioxidants. Renal morphological abnormalities of diabetic rats were markedly ameliorated by E.superbum. These results suggest that the antioxidant effect of E. superbum could ameliorate oxidative stress and delay/prevent the progress of diabetic nephropathy in diabetes mellitus.