In vitro evaluation of cell viability and expression profile of growth factors in mouse Sertoli cells exposed to Delta-9-tetrahydrocannabinol: a mechanistic insight into the cannabinoid-induced testicular toxicity.

The potentially adverse effects of cannabis (marijuana), a common leisure compound, on male reproductive performance are a reason for concern. δ-9-tetrahydrocannabinol (THC), the primary active component of marijuana alters testicular cells' proliferation and function which affects male fertility and causes testicular cells dysfunction and apoptosis. The main objective of this study was to investigate the possible mechanism underlying the toxic effects of THC with a mechanistic insight into Sertoli cell-based reproductive dysfunction. The Mus musculus Sertoli cell line (TM4) was cultured and exposed to different concentrations of THC and, MTT (3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was then performed for evaluating cell viability. The expression of caspase-3 gene and genes related to growth factors were analyzed by real-time RT-PCR. Western blotting was performed for evaluating protein expression level. THC concentration-dependently decreased the TM4 viability with a significant effect starting at concentration of 1 µM and reaching about 75% of the control level at the concentration of 50 µM (IC25). Moreover, caspase-3 mRNA expression levels significantly increased while growth factors mRNA levels decreased in THC-exposed cells compared to unexposed cells. There was also a significant reduction in related protein levels in THC group. Administration of the THC promotes cytotoxic and apoptotic effects on TM4 cells partly through down-regulation of growth factors expression. Increased apoptosis, over expression of caspase-3, and down-regulation of growth factors expression in Sertoli cells exposed to THC may be a reflection of THC-induced testicular toxicity, which may be partly involved in infertility associated with marijuana smoking or medical cannabis use.

Effect of orally-administrated thymoquinone during pregnancy on litter size, pentylenetetrazol-induced seizure, and body weight in rat offspring.

OBJECTIVES: This study aimed to assess the impact of orally-administrated thymoquinone (TQ) during pregnancy on litter size, pentylenetetrazol-induced seizure, and body weight in rat offspring. MATERIALS AND METHODS: In this experimental study, 64 pregnant rats were divided into groups according to the doses of TQ (0,10, 40, and 80 mg/kg) and gestational week (GW2 and GW3) of TQ administration. After parturition, the pups were counted, weighed, and assessed for pentylenetetrazol (PTZ)-induced seizure on postnatal days 14 (P14) and 21 (P21). RESULTS: In GW2 treated rats, TQ 40 mg/kg decreased seizure stages compared with control only on P14 while seizure duration significantly decreased on P14 and P21. On P14, 40 mg/kg TQ increased latency to the first seizure but decreased it on P21. In addition, 40 mg/kg dose decreased body weight (BW) on P1, P14, and P21 compared with 10 mg/kg dose and control groups. The dose of 80 mg/kg led to a complete pregnancy loss. In GW3 treated rats, only 10 mg/kg TQ decreased the seizure stages on P14 and P21. None of the doses had a significant effect on seizure duration and latency. TQ 40 and 80 mg/kg led to a low birth weight while increased BW on P14 and P21. A 50% decrease in litter size was observed in 80 mg/kg treated rats. CONCLUSION: Prenatal TQ may have anticonvulsant effects. The effects of TQ on BW of offspring depend on its dose and administration time. Also, a high dose of TQ at GW2 can be severely toxic for pregnancy.

Co-administration of retinoic acid and atorvastatin mitigates high-fat diet induced renal damage in rats.

Obesity causes many problems such as cardiovascular and chronic kidney diseases. The aim of this study was to evaluate the efficacy of retinoic acid and atorvastatin co-administration in kidneys protection against high-fat diet induced damage. Twenty-five male Wistar rats (200.00 ± 20.00 g) were divided into five groups: 1) Control (standard diet), 2) High-fat diet (cholesterol 1.00%, 75 days), 3) High-fat diet + atorvastatin (20.00 mg kg-1 per day, orally, on the 30th day, for 45 consecutive days), 4) High-fat diet + retinoic acid (5 mg kg-1 per day, orally, on the 30th day, for 45 consecutive days), and 5) High fat diet + atorvastatin and retinoic acid. At the end, blood and tissue samples were collected for biochemical and histological analyses. The results showed that atorvastatin and retinoic acid alone and in combination decreased cholesterol and low-density lipoprotein and increased high-density lipoprotein in high-fat diet. Also, atorvastatin - caused total antioxidant capacity increase and protein carbonyl content decrease the in the renal tissue. Atorvastatin also prevented high-fat diet-induced renal histological injury. Treatment with atorvastatin significantly mitigates high-fat diet-induced renal changes probably due to its potent antioxidant and lipid-lowering effects. The effect of retinoic acid in renal protection in a high-fat diet is far less than that of atorvastatin. The protective effect of the combination of these two agents in the high-fat diet on the kidneys seems to be due to the effect of atorvastatin.

Protective role of grape seed proanthocyanidin antioxidant properties on heart of streptozotocin-induced diabetic rats.

Grape seed proanthocyanidin (GSP) bears a very powerful antioxidant effects. Studies demonstrated that proanthocyanidins protect against free radicals mediated cardiovascular and renal disorders. The present study was designed to assess the effect of GSP on the heart of diabetic rats. Forty rats were divided into four groups of 10 animals each: Group I: control, Group II: control group were given GSP, Group III: diabetic group, Group IV: diabetic group treated with GSP. Diabetes was induced by a single dose of streptozotocin, and then GSP (200 mg kg(-1) body weight) was administrated for four weeks. Blood glucose, glycosylated hemoglobin (HbA1c) and also the levels of lipid peroxidation and antioxidant enzymes were examined in the heart tissues of all groups. Oral administration of GSP to diabetic rats significantly reduced (p < 0.05) heart weight, blood glucose, HbA1c and lipid peroxidation level, but increased (p < 0.05) body weight and activities antioxidant enzymes when compared to diabetic group. The results indicated that GSP could be useful for prevention or early treatment of cardiac disorder caused by diabetes.

Hydrogen sulfide ameliorates the kidney dysfunction and damage in cisplatin-induced nephrotoxicity in rat.

Hydrogen Sulfide (H2S) prevents and treats a variety of disorders via its cytoprotective effects. However, the effects of H2S on rats with cisplatin (CP) nephrotoxicity are unclear. The aim was to study the effects of H2S on rats with CP nephrotoxicity. Thirty male Sprague-Dawley rats were divided into three groups: control group, nephrotoxic group received single dose of CP (6 mg kg(-1)) and nephrotoxic groups that received single dose 100 µmol kg(-1) NaHS. On fifth day after injection, urine of each rat was collected over a 24-hr period. Animals were sacrificed 6 days after CP (or vehicle) treatment, and blood, urine, and kidneys were obtained, prepared for light microscopy evaluation, lipid peroxidation content and laboratory analysis. The results showed that plasma urea (226%), creatinine (271%), renal lipid peroxidation content (151%), Na and K fractional excretion, urine protein, volume and kidney weight in CP nephrotoxic rats were significantly higher and urine osmolarity and creatinine clearance lower than in controls. Increases of the proximal tubular cells apoptosis and mesangial matrix in CP nephrotoxicity group rats were observed. Hydrogen sulfide reversed the CP-induced changes in the experimental rats H2S prevented the progression of CP nephrotoxicity in rats possibly through its cytoprotective effects such as antioxidant properties.