The Effect of Thymus vulgaris on Hepatic Enzymes Activity and Apoptosis-Related Gene Expression in Streptozotocin-Induced Diabetic Rats.

Many diseases, including diabetes, are involved in the development of liver disorders through changes in the expression of genes such as apoptosis-related genes. In the present study, the effect of Thymus vulgaris (T. vulgaris) on hepatic enzyme activity and apoptosis-related gene expression in streptozotocin (STZ)-induced diabetic rats was examined. In this study, 50 adult male Wistar rats weighing approximately 200-220 g were divided into five groups. Diabetes was induced by an intraperitoneal injection of STZ (60 mg/kg). Following 18 days, all the animals in different groups were weighed and blood samples were taken from their cardiac veins. Gas chromatography-mass spectrometry (GC-MS) analysis revealed 45 different compounds in the T. vulgaris, including thymol (39.1%), p-cymene (20.63%), and γ-terpinene (14.85%). The results showed a significant increase in liver enzymes (aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP)) in diabetic or STZ mice compared to the control group (healthy mice) (P < 0.0001). The levels of AST, ALT, and ALP in rats treated with 200 mg/kg and 400 mg/kg of T. vulgaris extract showed a significant decrease in these enzymes in comparison with diabetic rats (P < 0.0001). The expression of caspase 3 and 9 genes in the groups treated with thyme significantly decreased compared to diabetic mice (P < 0.0001), and the expression of B-cell lymphoma-2 (Bcl-2) in the group receiving 400 mg/kg of thyme significantly increased compared to diabetic mice (P < 0.0001). Due to its antioxidant compounds, thyme improves the liver tissue cells in STZ-induced diabetic mice by reducing caspases 3 and 9 as well as increasing Bcl-2.

Preventive Effects of Sinigrin Against the Memory Deterioration in the Pentylenetetrazole-Kindled Male Wistar Rats: Possible Modulation of NLRP3 Pathway.

Mainly found in brussels sprouts, broccoli, and black mustard seeds, sinigrin (2-propenyl glucosinolate) has enjoyed some attention currently for its effects on health and disease prevention. The present research design is aimed at investigating the effects of sinigrin on inflammation, oxidative stress (OS) and memory. Randomly, six groups of male Wistar rats were categorized into the control and experimental groups. The experimental groups were treated with sinigrin (10 and 20 mg/kg, orally). The control positive group was given the pentylenetetrazole (PTZ) treatment and the control negative one was given normal saline. All groups were kindled by the sub-threshold dose (35 mg/kg, i.p.) of PTZ for 12 times in one month. When the kindling procedure was done, the seizure behaviors and the behavioral function were evaluated. For cognitive parameters, the shuttle box test was employed. When the experiment was terminated, the rats were euthanized and their blood serum as well as brain samples were isolated for respective measuring of OS and gene expression parameters. The treatment with sinigrin significantly delayed the appearance of the seizure symptoms in comparison to that of the PTZ group. It also significantly increased the memory parameters like retention latency and the total time having been spent in the light compartment in the epileptic rats. In addition, sinigrin increased the superoxide dismutase and catalase levels. Treatment with sinigrin suppressed the Il1b and Nlrp3 gene expression at hippocampal level. In sum, sinigrin prevents inflammation, OS and memory impairment against the PTZ-kindling epilepsy in rats.

Rapamycin alleviates memory deficit against pentylenetetrazole-induced neural toxicity in Wistar male rats.

Numerous studies have reported that epilepsy causes memory deficits. The present study was aimed at studying the effect of rapamycin against the memory deficiency of the pentylenetetrazole (PTZ)-kindled animal model of epilepsy. In the present experiment, we randomly chose thirty male rats from the species of Wistar and categorized them in groups of control and experiment (6 for each group). The groups of experiment received the injection of rapamycin (0.5, 1 and 2 mg/kg) intraperitoneally (i.p.) and the group of control received normal saline (0.9%) treatment. Through the PTZ's sub-threshold dose (35 mg kg-1, i.p.), all groups were kindled 12 times. Passive avoidance test (PAT) was used for gauging the memory function and the seizure behaviors after the kindling procedure. The rodents were sacrificed at the end of the trial and their brains were scooped for measuring the expression of Gabra1 and Pras40 genes. Statistical analysis unveiled that rapamycin delayed the kindling development and the onset of seizures which are tonic-clonic. Moreover, the administration of rapamycin significantly prevented memory dysfunction in epileptic rats. Finally, it was shown that rapamycin resulted in an increase in the expression levels of Gabra1 and Pras40 genes at the brain tissues. The current research design indicated that rapamycin has beneficial effects for the prevention of memory impairment against PTZ-kindling epilepsy in rats. Such promising outcomes could be attributed to its impact on the Gabra1 and Pras40 genes.

Rapamycin attenuates depression and anxiety-like behaviors through modulation of the NLRP3 pathway in pentylenetetrazole-kindled male Wistar rats.

BACKGROUND: There is cumulative evidence that shows the effect of epilepsy on behavioral conditions like anxiety and depression. OBJECTIVES: The effects of rapamycin on anxiety and depression caused by pentylenetetrazole (PTZ) in the rat and possible underlying mechanisms were evaluated. METHODS: Male Wistar rats were divided into experimental and control groups. The experimental groups were treated with intraperitoneal (i.p.) injection of 0.5, 1, and 2 mg/kg of rapamycin, while the control group received normal saline only. Kindling was induced by sub-threshold dose (35 mg/kg, i.p.) of PTZ for one month. When the kindling procedure was done, the seizure behaviors and the behavioral function were evaluated. For anxiety parameters, the elevated plus maze (EPM) was used. The forced swim test was employed to assess the antidepressant potential. At the end of the experiment, rats were euthanized and the blood serum and brain samples were isolated for respective measurement of oxidative stress and gene expression parameters. RESULTS: Rapamycin delayed the development of kindling and the onset time of seizures. Rapamycin administration reduced immobility time in the FST, exerting antidepressant-like activity. In the EPM test, rapamycin produced an anxiolytic-like effect. In addition, rapamycin increased the catalase and superoxide dismutase levels in the serum and significantly decreased the gene expression of I11b and Nlrp3 compared to the PTZ group. CONCLUSION: Our results showed that the inhibitory effect of mTOR inhibitor (rapamycin) on reactive oxygen species production during NLRP3 inflammasome activation could bring about behavioral alterations in anxiety and depression.

The Effects of Exercise on Expression of CYP19 and StAR mRNA in Steroid-Induced Polycystic Ovaries of Female Rats.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is the most frequent female endocrine disorder that affects 5-10% of women. PCOS is characterized by hyperandrogenism, oligo-/anovulation, and polycystic ovaries. The aim of the present research is to evaluate the expression of steroidogenic acute regulatory protein (StAR) and aromatase (CYP19) mRNA in the ovaries of an estradiol valerate (EV)-induced PCOS rat model, and the effect of treadmill and running wheel (voluntary) exercise on these parameters. MATERIALS AND METHODS: In this experimental study, we divided adult female Wistar rats that weighed approximately 220 ± 20 g initially into control (n=10) and PCOS (n=30). Subsequently, PCOS group were divided to PCOS, PCOS with treadmill exercise (P-ExT), and PCOS with running wheel exercise (P-ExR) groups (n=10 per group). The expressions of StAR and CYP19 mRNA in the ovaries were determined by quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR). Data were analyzed by one-way ANOVA using SPSS software, version 16. The data were assessed at α=0.05. RESULTS: There was significantly lower mRNA expression of CYP19 in the EV-induced PCOS, running wheel and treadmill exercise rats compared to the control group (P<0.001). Treadmill exercise (P=0.972) and running wheel exercise (P=0.839) had no significant effects on CYP19 mRNA expression compared to the PCOS group. mRNA expression of StAR in the ovaries of the PCOS group indicated an increasing trend compared to the control group, however this was not statistically significant (P=0.810). We observed that 8 weeks of running wheel and treadmill exercises could not statistically decrease StAR mRNA expression compared to the PCOS group (P=0.632). CONCLUSION: EV-induced PCOS in rats decreased CYP19 mRNA expression, but had no effect on StAR mRNA expression. We demonstrated that running wheel and moderate treadmill exercise could not modify CYP19 and StAR mRNA expressions.