الفهرس 
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Abstract
Diethylnitrosamine (DEN) and Benzo[a]pyrene (BP) is carcinogenic contaminant. Liver injury and organ toxicity has been observed in human and laboratory animals as aresult of treatment with DEN. The present study has been conducted to evaluate the preventive role of algal ethanolic extracts of Spirulina versicolor and Enteromorpha flexuosa against DEN/BP-induced hapatotoxicity and nephrotoxicity as well as carcinogenicity in albino rats.
Animals were divided into 4 groups; each is 12 rats at two periods of time (2 weeks and 8 weeks). Six rats of each group were sacrificed at the end of 2nd and 8th weeks of DEN-administration. The experimental groups were designated as follows:
group 1 (Normal): It received intraperitoneal (ip) normal saline and was orally administered 1% carboxymethylcellulose (CMC).
group 2 (DEN/BP Control): The rats of this group received a single ip dose of 200mg/kg b. w. DEN (dissolved in 0.9% saline) and benzo[a]pyrene (dissolved in corn oil) at dose level of 50 mg/kg b. w. twice/week for 6 weeks beginning from the 3rd week of the experiment. The rats of this group were orally administered the equivalent volume of 1% CMC daily for 8 weeks beginning from the starting period of the experiment.
group 3 (DEN/BP + S. versicolor): It received 200mg/kg b.w. DEN and 50 mg/kg b.wt benzo[a]pyrene twice/week as group 2 and orally supplemented S. versicolor ethanolic extract (25mg/kg b. w./day) dissolved in 5ml 1% CMC through the entire experimental period.
group 4 (DEN/BP + E. flexuosa): The rats of this group received 200mg/kg b. w. DEN and 50 mg/kg b. w. benzo[a]pyrene twice/week and orally supplemented E. flexuosa ethanolic extract (25mg/kg b. w./day) dissolved in 5ml 1% CMC through the entire experimental period.
By the end of the experimental periods (2 and 8 weeks), fasted rats in all groups were sacrificed under diethyl ether anaethesia. Blood samples were collected from each rat, left to coagulate, then centrifuged and the clear supernatant sera were quickly removed for subsequent biochemical analysis for liver function parameters (ALT, AST, γ-GT, total bilrubin,total protein and albumin), kidney function parameters that include (urea and creatinine), pro-inflammatory cytokine (TNF-α) and tumor marker alpha fetoprotein (AFP) in serum. Liver and kidney tissues were quickely excised after dissection of the animals. Fresh liver and kidney samples were immediately removed from each animal and cut into two pieces; one of them was fixed in 10% neutral buffered formalin for histological examination. The other part of these tissues was homogenized (0.5g tissue/5ml 0.9% saline) for determination of lipid peroxidation (LPO), glutathione (GSH) content and activity of antioxidant enzymes including glutathione–S-transferase (GST) glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT).
Results showed that DEN/BP-administration caused a marked rise in serum (ALT, AST and γGT activities and total bilrubin concentration) together with lowered serum total protein and albumin levels and elevated TNF-α and AFP concentrations. Kidney function markers (urea and creatinine) levels in serum were also increased. Antioxidant defense markers (GSH, GST, GPx, SOD and CAT) were decreased significantly in DEN/BP-administered rats; however, lipid peroxidation (LPO) was increased in these animals. Significant histopathological alterations in both liver and kidney tissues were also observed in the DEN/BP-administered animals.The precarcinogenic lesions of liver and kidney were reduced or disappeared as a result of treatment of DEN/BP-administered rats with S. versicolor and E. flexuosa ethanolic extracts seemed to exhibit preventive effects against hepatonephrotoxicity and carcinogenicity due to their antioxidant properties and their ability to reduce lipid peroxidation.
Taken these data together, it can be concluded that both S. versicolor or E. flexuosa ethanolic extracts have potential preventive effects against DEN/BP-induced hepato and nephrotoxicity through their anti-inflammatory, anti-carcinogenic and antioxidant efficacies.