Journal of Basic & Clinical Pathophysiology
Volume:11 Issue: 1, Winter-Spring 2023

This study aimed to determine the effect of metformin (MET) on semen profile and hormonal levels in a model of varicocele in rats.

Sixty male Wistar rats were allocated into 5 treatment groups as control and varicocele groups. In groups 3-5, varicocele animals received MET (25, 50 and 100 mg/kg) for 42 days. At the end of the study, semen evaluations and serum testosterone and luteinizing hormone and follicle stimulating hormone levels were measured.

Experimental varicocele significantly decreased total sperm count and sperm motility and increased non-motile sperms compared to the control group (p<0.05). Metformin administration (50 and 100 mg/kg) significantly increased total sperm count and sperm motility and decreased non-motile sperm as compared to the varicocele group (p<0.05). In addition, experimental varicocele significantly decreased testosterone and luteinizing hormone and follicle stimulating hormone levels as compared to the control group (p<0.05). Metformin administration (50 and 100 mg/kg) significantly increased testosterone and luteinizing hormone and follicle stimulating hormone levels as compared to the varicocele group (p<0.05).

These results suggested that metformin has positive role against varicocele in the rat.

This study aimed to determine anti-depressant effect of α-pinene on gonadectomized-related behavior in male rats.
Thirty adult male Wistar rats were assigned to 5 experimental groups. In the control group, surgeries were identical but testes were not clamped, ligated or excised. In the sham control, surgeries were identical with no treatment. In the imipramine group, rats were administered with imipramine (15 mg/kg) followed by castration for 2 weeks. In groups 4 and 5, following castration, rats were i.p. injected with 𝛼-pinene (0.5 and 1 mg/kg) for 2 weeks, respectively. Following recovery, forced swimming test (FST), tail suspension test (TST), and open field test (OFT) were performed and serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activity were determined.
According to the data, immobility time significantly increased following castration compared to control group (p<0.05). Administration of the imipramine significantly decreased immobility time compared to control group (p<0.05). Treatment with 𝛼-pinene (0.5 and 1 mg/kg) significantly decreased immobility time in comparison with sham control group (p<0.05). Number of crossings in the OFT significantly diminished following castration and treatment with 𝛼-pinene (0.5 and 1 mg/kg) increased number of crossings in the OFT compared to sham control group (P<0.05). Serum MDA significantly increased while SOD, GPX and CAT decreased following castration compared to the control group (p<0.05). Administration of the 𝛼-pinene (0.5 and 1 mg/kg) significantly improved serum MDA, SOD, GPX and CAT production compared to the sham rat (p<0.05).
These results suggested that 𝛼-pinene has anti-depressant and antioxidant effects in gonadectomized-related behavior in male rats

Alzheimer's disease (AD) is the most prevalent cause of dementia globally, with its incidence continuing to increase. Cis phosphorylated tau (Cis p-tau) is postulated as the earliest detectable pathogenic marker in AD and as a novel diagnostic and therapeutic factor. This study was conducted to evaluate stage of AD patients based on plasma level of Cis p-tau.
Target population (65-80 years) was chosen from people with AD who visited the neurology clinic of Firouzgar hospital. Selection of cases was according to their medical history and they were divided into control and AD groups at two early and late stages. Individual's cognitive performance was evaluated using Mini-Mental State Exam (MMSE) and Clinical Dementia Rating (CDR) tests besides measurement of plasma level of Cis p-tau.
The results obtained for this study showed that besides significant difference in cognitive indices between control group and two groups of AD patients at early and late stages of the disease, plasma level of Cis p-tau is significantly higher in AD groups (especially in late stage AD group) as compared to the control and healthy group (p<0.05).
It seems that routine measurement of plasma Cis p-tau in AD patients may be of clinical diagnostic value to differentiate AD stages and to evaluate efficacy of used therapies. However, further large-scale research studies are still required to affirm this issue.

Morphine is one of the most powerful analgesic substances that is widely used in the clinic. This substance increases nitric oxide (NO) levels and blood flow to the ovary and ruptures the follicle wall. Damaged tissue can be repaired under the influence of epidermal growth factor (EGF). This study aimed to investigate the effect of short-term administration of morphine on the intensity of EGF receptor (EGFR) and iron deposition in ovarian tissue in Wistar rats.
In this study, 16 female Wistar rats were randomly divided into two groups. The control group (n=8) received 1 ml/kg of saline twice, once a day intraperitoneally (i.p.). The experimental group received 5 mg/kg morphine sulfate (i.p.) once a day for two consecutive days. 24 hours after the last injection, rats were anesthetized with ketamine and xylazine, and the ovaries and uterus were isolated for histological study. Iron deposition was investigated with the help of potassium ferricyanide staining and EGF receptor (EGFR) density was determined by immunohistochemistry method.
Hemochromatosis in the form of blue iron deposits was shown significantly in the group receiving morphine as compared to the control group. Also, a higher concentration of EGFR was observed in the group treated with morphine than in the control group, which indicates the involvement of EGF in ovarian hyperemia.
Short-term use of morphine can cause hemochromatosis as a result of iron deposition in the ovary which is associated with hyperemia due to high NO levels induced by EGF.

Prolactin is a necessary factor for lactation and synthesis of milk constituent. Progesterone (P4) and 17β-estradiol (E2) are inhibitory factors for lactation. Orexin is involved in regulating the metabolism and lipid synthesis. Present study investigated the orexin B receptor antagonist and steroid hormone effects on milk lactose synthesis. Thirty Wistar lactating rats were used. Lactating animals in the group 1-4 received saline, 1, 2 or 4 µg of orexin antagonist. Lactating animals of the groups 5 and 6 received 4 µg of orexin antagonist plus 1 µg of 17-β estradiol (E2) or 4 mg of progesterone (p4). Blood and tissue samples were collected at 60 and 180 minutes of injections. Blood samples were measured for prolactin concentrations and tissue samples were examined for alpha lactalbumin (Lalba) and beta-1,4-galactosyltransferase 1 (B4galt1) gene expression in the mammary gland by RT-PCR technique. Injection of orexin antagonist significantly increased the percentage of milk lactose, plasma prolactin and Lalba gene expression in comparison to control group. Injections of E2 or P4 inhibited the increased effects of orexin antagonist on mean milk lactose percentage, prolactin and Lalba gene expression in comparison to orexin antagonist group. Injections of all drugs did not alter the mean B4galt1 gene expression. Stimulatory effects of orexin antagonist on milk production may be partly due to the increased prolactin concentration and Lalba gene expression. The mechanism by which the steroid hormones supress the orexin antagonist-induced lactose synthesis may be mediated partly via inhibiting the prolactin production.

Alzheimer’s disease (AD) as the most common neurodegenerative disorder. Klotho is an anti-aging protein with important roles in neurodegenerative disorders. This study was done to evaluate the expression of klotho gene and protein in the plasma of AD patients treated with blood pressure control drugs (inhibitors of angiotensin-converting enzyme (ACE)) or blood lipids control drug (simvastatin).

Target population was selected from people with AD who visited the neurology clinic of Firouzgar hospital. The tested groups included the control group, Alzheimer's group, Alzheimer's group treated with blood pressure control drugs, and Alzheimer's patients group treated with blood lipid control drug. Expression of klotho gene and protein in the plasma of studied groups was determined using real-time PCR and ELISA techniques and the individual's cognitive disorders were also evaluated using Mini-Mental State Exam (MMSE) and Clinical Dementia Rating (CDR) tests.

The results obtained in this study showed that in addition to the significant difference in cognitive indices between the control groups and three groups of Alzheimer's patients, the level of klotho gene and protein expression was also lower in three groups of Alzheimer's patients compared to healthy group. However, there was no significant difference (p>0.05) between the Alzheimer's group and the two Alzheimer's groups treated with blood pressure or blood lipid control drugs.

Drugs controlling blood pressure or blood lipids in Alzheimer's patients possibly have no significant effect on the level of klotho protein. Obviously, more studies are needed in this field.

The role of the central nervous system in pain control is prominent via the regulation of neuropeptides. Plant derivatives such as trans-anethole could be effective due to analgesic properties. The present study investigated the analgesic effect of trans-anethole via modulation of hypothalamic orexin and melanin-concentrating hormone (MCH) gene expression in rats.

Twenty male Wistar rats (180-200 g) grouped into four groups of five rats (n=5). To induce pain, 50 μl of formalin was injected into the hind paws of the animals. The intact and formalin control groups received saline. Formalin induced pain groups received 150 or 250 mg/kg of trans-anethole. Pain score was evaluated by performing the formalin test. The hypothalamic samples were removed to analyze the gene expression levels via real-time PCR technique.

The pain score decreased in rats receiving 150 or 250 mg/kg trans-anethole compared to formalin control group. The relative gene expression of Orexin and MCH significantly increased in the formalin group compared to the intact rats. Injection of 150 or 250 mg/kg trans-anethole significantly reduced the relative gene expression of orexin and MCH in formalin induced pain groups compared to the formalin control rats.

Trans anethole caused downregulation of hypothalamic orexin and MCH gene expression due to its pain relieving properties. So, analgesic effects of trans anethole may be mediated via central mechanism.