دکتر عباسعلی کریمپور ملکشاه

Cyclophosphamide (CP) is an alkylating anticancer drug and one of the most successful drugs with a wide range of clinical activities. This drug has toxic effects on most organs, especially kidney tissue. Piperine, as a flavonoid, has antioxidant, anti-inflammatory, and anti-apoptotic properties. The purpose of the present study is to investigate the antioxidant effect of piperine (PIP) on nephrotoxicity following cyclophosphamide (CP) by tissue, serum, and histopathological biochemical evaluation.

In this experimental study, 48 adult male BALB/c mice aged 6-8 weeks and weighing 30-35 grams were divided into 6 groups, the control group (C), the group receiving cyclophosphamide (CP) with a dose of 200mg/kg, the group receiving piperine (Pip) with a dose of 5mg/kg, the group receiving piperine (Pip) with a dose of 10mg/kg, the group receiving cyclophosphamide and piperine at a dose of 5mg/kg (CP+Pip) and the group receiving cyclophosphamide and piperine with A dose of 10mg/kg (CP+Pip) was used. CP was administered on the third day of the study. Piperine was prescribed for 7 days in the form of pre-treatment and post-treatment. On the eighth day of the study, histochemical (GSH and MDA), histopathology, and serum biochemical evaluations were performed. Then, the data were analyzed with GraphPad Prism software one-way ANOVA and Tukey's post hoc tests.

CP induced oxidative stress with a significant decrease in GSH level (P<0.001) and increased MDA level (P<0.0001). On the other hand, administration of PIP with two doses of 5 and 10 mg/kg in mice receiving CP could significantly reduce the amount of MDA (respectively: P˂0.001, P˂0.001) and increase the amount of GSH compared to the mice that only received CP (respectively: P˂0.05, P˂0.05). In mice receiving CP, a significant increase (P<0.05) in the amount of urea and creatinine was shown compared to mice in the control group. In contrast, groups treated with piperine (5 and 10 mg/kg body weight) before and after CP administration significantly (P<0.0001) improved the kidney damage towards normalization compared to mice treated with CP alone and histopathological evaluation confirmed this finding. The effect of piperine was seen in a dose-dependent manner in this study. Thus, in the group treated with cyclophosphamide, the loss of epithelial cells and the widening of the lumen of the distal and proximal convoluted tubules, the contraction of the glomerular network, and the expansion of Bowman's capsule between the visceral and parietal layers were seen. The administration of piperine improved these changes, and the 5 mg/kg dose showed a more effective role.

The general results of the present study showed that before and after the administration of piperine in rats treated with CP, it reduces nephrotoxicity caused by CP and has a positive effect on improving kidney function in connection with its antioxidant effect. Piperine can be suggested as a potential candidate for cancer patients undergoing chemotherapy.

Benzo[a]pyrene (BaP) is an environmental pollutant that has genotoxic and carcinogenic effects. Atorvastatin (ATV), as a lipid-lowering drug, has antioxidant, anti-inflammatory and anti-apoptotic properties. This study investigated the effects of ATV on chronic liver and kidney damage induced by BaP.

In this experimental study, adult female rats were randomly divided into seven groups (n= 8 per group), including control group, olive oil group, ATV group (10 mg/kg), BaP groups (10 and 20 mg/kg), and ATV + BaP groups (10 and 20 mg). The drugs were administered by oral gavage for ten consecutive days. Histopathologic evaluation of the liver and kidney tissues was done one month after drug administration.

Histopathologic changes in both liver and kidney tissues such as inflammatory cell infiltration, plasma leakage, reduced acidophilia of hepatocytes, and renal tubular cells were seen in the groups receiving BaP. Findings showed that BaP at 20 mg/kg caused more serious harm than that at 10 mg/kg. ATV treatment protected structural changes in liver and kidney tissues.

Current study showed that destructive effects of benzopyrene remain until one month after administration. The protective effects of atorvastatin against benzopyrene-induced hepatotoxicity were confirmed over time.

The anthracyclin drug doxorubicin (Adriamycin) is one of the most effective antineoplastic agents، and widely used to treat a number of malignancies. However، its use has been restricted due to the dose-dependent cardiotoxicity. The mechanisms of Doxorubicin - induced cardiotoxicity is not entirely clear. This study investigates the effect of Doxorubicin on Bcl2 and Bax genes expression as key molecules that involve in intrinsic pathway of apoptosis in rat heart.

In this experimental study Doxorubicin administration، male Wistar rats were exposed to intraperitoneal injections (2. 5 mg/kg، six times for 2 weeks، n=20). Animals were randomly assigned to the healthy untreated control (n=10) and to the Doxorubicin treatment groups (n=10). Three weeks after completion of treatment myocardial fibrosis، Bcl2 and Bax genes expression were investigated by Masson’s trichrome staining and Real Time- PCR analysis respectively. Statistical analysis was performed using the SPSS-16 and independent samples t-test، Mann-Whitney and Kaplan-Meyer method.

Masson’s trichrome staining showed that Doxorubicin increased fibrosis in the cardiac muscle (16. 4±1) in compare to control group (1±0. 79). Real Time- PCR analysis showed that Doxorubicin decreased Bcl2 expression levels (0. 1±0. 07) and increased Bax expression levels (2. 1±0. 1) in the myocardium in compare to control group (P<0. 01).

This study showed that administration of Doxorubicin increase interstitial fibrosis of myocardium and Bax expression levels and decrease Bcl2 expression that are the key genes of mitochondria-dependent apoptotic pathway.