Liver cancer, predominantly hepatocellular carcinoma (HCC), represents a complex and fatal malignancy driven primarily by oxidative stress and inflammation. The chemopreventive effect of omega-3 on inflammatory markers and oxidative damage, caspase-3, antioxidant status and histopathological alterations in hepatic tissue in N-nitrosodiethylamine (DEN)-induced HCC in male rats was investigated. To induce HCC, rats were given DEN (200 mg/kg b.wt.,i.p) three times at a 15 day interval. 75 rats were divided into five equal groups. Control group, DEN group, DEN + ω3 protected group received omega-3 (270mg/kg b. wt/day) orally 4 weeks before DEN injection and continued to 13 weeks, DEN + ω3 treated group firstly injected with DEN and orally treated with omega-3 from the 8 th week till the end of the experiment (13 th week) and normal -ω3 group received omega-3. Blood samples and liver tissues were collected at 13 th week. DEN-induced HCC significantly decreased SOD and CAT activities in liver tissue. However, a marked increase in liver tissue L-MDA, DNA fragmentation, caspase-3 and Nf-kB P65 and in serum AFP, IL-6 and TNF-α levels were observed in DEN injected rats. Initiation of HCC was demonstrated by histopathological examination of hepatic tissue in DEN injected group. Histopathological examination confirmed the pathological improvement in the liver of rats in omega -3 protected and treated groups. In conclusion, omega-3 demonstrates antiinflammatory property by suppression of TNF-alpha and IL-6 due to inhibition of NF-kB p65 and exerts its chemopreventive effect on liver carcinogenesis. These data suggest that omega-3 exhibited significant protection against DEN-induced HCC, which might be related with the enhancement of the antioxidant activity and the induction of apoptosis.

Cyclosporine A (CsA) is a strong immunosuppressive drug, but its use is frequently accompanied by severe renal toxicity. The potential reno-protective effect of Thymoquinone (TQ) against CsA-induced nephrotoxicity in rats was assessed. Thirty adult white male albino rats were divided into three equal groups. Group I: (Normal control), received no drugs, Group II: (CsA treated), rats received oral dose of Cyclosporine A (25 mg/kg b. wt./day) for 21 days. Group III: (TQ protected + CsA), received Thymoquinone (10 mg/kg b. wt./day) orally 7 days before and during 21 days of CsA treatment. The obtained results showed a significant increase in the concentration of urea and creatinine in serum and L-MDA level in kidney tissue with marked decrease in renal catalase activity and GSH concentration in CsA treated rats. Moreover, a significant down-regulation in Bcl-2 and up-regulation of NF-κB, PAI-1, Caspase-3 and p53 gene expressions levels were observed in kidney tissues of CsA treated rats. Also, various histopathological alterations were detected in kidneys of CsA treated rats. Meanwhile, TQ potentially improved renal function and oxidative alterations related to CsA near its normal ranges. Interestingly, histopathological findings supported that TQ markedly attenuates harmful effects that CsA induced and protected kidney. Our research could conclude that, TQ has an ameliorating role as potent antioxidant, anti-inflammatory and anti-apoptotic agent via inhibition of inflammatory (NF-κB, PAI-1) and apoptotic (Caspase-3, p53) signaling pathway in modulation of CsA-induced nephrotoxicity.

Cyclosporine A (CsA) is a drug used as immunosuppressive agent in organ transplant and nontransplant medicine. The main secondary effect results from CsA treatment is nephrotoxicity. A protective effect of Grape seed proanthocyanidin extract (GSPE) against CsA-induced nephrotoxicity in rats was assessed. Thirty male rats were divided into three equal groups. Group I: (Normal control), received no drugs, Group II: (CsA treated), rats received oral dose of CsA (25 mg/kg b.wt/day) for 21 successive days. Group III: (GSPE protected+ CsA), rats received GSPE (200 mg/kg b.wt/day) orally 7 days before and during 21 days of CsA treatment. The obtained results showed a significant increase in serum urea and creatinine concentration in addition to L-MDA levels in kidney tissue while a marked decrease in renal catalase activity and GSH concentration in CsA treated rats. Moreover, a significant down-regulation in Bcl-2 and up-regulation of NF-κB, PAI-1, Caspase-3 and p53 gene expressions were observed in kidney tissues of CsA treated rats. Meanwhile, GSPE potentially improved renal function and oxidative alterations related to CsA near its normal ranges. Also, various histopathological alterations were detected in kidneys of CsA treated rats. Interestingly, histopathological findings supported that where GSPE markedly attenuated the harmful effects induced by CsA and protected kidney tissues. Our research could conclude that, GSPE has an ameliorating role as potent antioxidant, anti-inflammatory and anti-apoptotic agent via inhibition of inflammatory (NF-κB, PAI-1) and apoptotic (Caspase-3, p53) signaling pathway in modulation of CsAinduced nephrotoxicity.