الملخص
Endosulfan toxicity affects the nervous system as well as immunological functions. It also causes oxidative stress and subsequent mitochondrial dysfunction. In the present study, we tried to evaluate the protective effects of melatonin on endosulfan (END) induced immunological and biochemical changes in rats. Wistar rats (200-250 g, n=8/group) were immunized with fresh SRBC (0.5×109 cells/kg) and were exposed to END (4-16 mg/kg, orally), simultaneously exposed animals were treated with vehicle or melatonin (10 and 50 mg/kg) for 14 days. On day 15, their blood and spleen was collected for immunological assays and oxidative stress markers. Endosulfan (8 and 16 mg/kg) significantly suppressed (i) anti-SRBC antibody titer; (ii) footpad thickness; (iii) spleen PFC counts; and (iv) Th1 (IFN-γ) & Th2 (IL-4) and significantly increases serum TNF-α level as compared to controls (P <0.05 in all parameters). Endosulfan induced immunological changes were found associated with changes in oxidative stress markers as evidenced by the results of this study. Endosulfan, while significantly decreased GSH, SOD and CAT activity (P <0.05), it increased serum TBARS activities (P <0.001). These endosulfan induced changes in immunological and biochemical parameters were found significantly reversed by the treatment with melatonin (10 and 50 mg/kg) in a dose dependent manner by differential degrees. Results of the present immunological and biochemical data suggest the protective role of melatonin in endosulfan induced immunomodulation which is associated with oxidant/antioxidant imbalance.
الملخص
Background & objectives: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality. The objective of this study was to find out the differential expression of apolipoproteins (ApoAI and ApoAIV) in HCC and cases of liver cirrhosis and chronic hepatitis (controls) without HCC and to compare ApoAI and ApoAIV expression with alpha-foetoprotein (AFP), the conventional marker in HCC. Methods: Fifty patients with HCC and 50 controls comprising patients with liver cirrhosis (n=25) and chronic hepatitis (n=25) without HCC were included in this study. Total proteins were precipitated using acetone precipitation method followed by albumin and IgG depletion of precipitated protein using depletion kit. Proteins were separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The expression changes of ApoAI and ApoAIV were confirmed by western blotting using specific primary and secondary polyclonal antibodies followed by densitometric protein semi-quantitative estimation. ApoAI, ApoAIV and AFP were measured in the plasma samples by ELISA method. Results: Semi-quantitative densitometric image analysis of the western blot images and the comparison between HCC patients with those without HCC (control) revealed differential expression of ApoAI and ApoAIV. Levels of ApoAI were significantly higher in patients with HCC compared to controls without HCC (0.279�216 vs 0.171�091 and 0.199�014; P <0.001). Levels of ApoAIV were significantly lower in patients of HCC compared to controls without HCC (0.119�061 vs 0.208�07 and 0.171�16; P <0.01). ELISA assays of apolipoproteins (ApoAI and ApoAIV) revealed similar results of expression of ApoAI and ApoAIV as detected in western blotting densitometric image analysis. Interpretation & conclusions: Increased expression of ApoAI and decreased expression of ApoAIV in HCC patients compared to controls without HCC revealed the abnormalities in HCC. These molecules need to be studied further for their use as potential biomarkers in the future diagnostic tools along with other conventional biomarkers for screening of HCC cases. It needs further analysis in higher number of patient population.