RESUMEN
The present study was conducted to evaluate the potential gastric protective and therapeutic effects of ranitidine mucoadhesive hydrogel formulae against ethanol induced gastric ulceration in rats. Adult female albino rats weighing between 200-220 g ,75 rats for evaluation of mucoadhesiveness of hydrogel and 70 rats for evaluation of protective and therapeutic effect of ranitidine hydrogel. The seventy rats were randomly divided into two experiments, protective and therapeutic effects of newly developed ranitidine mucoadhesive hydrogel formulae containing polymer mixture of Chitosan and Hydroxypropyl methyl cellulose [HPMC] at ratio 9:1 [F1] or mixture of Sodium carboxymethyl cellulose [NaCMC] and HPMC at ratio 9:1 [F2]. Each experiment has five groups, seven rats each; group 1 serves as control and group 2 serves as ulcer control since received a single oral dose of absolute ethanol [5ml/kg body weight]. Group 3 ulcer group received an oral dose of ranitidine [27mg/kg], while groups 4 and 5 ulcer group received newly formulae of ranitidine F1and F2 respectively. In the present study some gastric parameters as ulcer index, total acidity, gastric volume and pH besides some biochemical parameters as alanine aminotransferase [ALT], aspartate aminotransferase [AST] and total antioxidant capacity [TAC], total protein [TP] level and alkaline phosphatase [ALP] activity were carried out at the end of the experimental period.The present study showed that F1 revealed more protective and therapeutic potency than F2 as it was significantly reduced ulcer index, total acidity, gastric volume and pH in comparison to ulcerated group [p<0.05]. Also, the biochemical markers ALT, AST and TAC were decreased significantly compared to ulcerated group in both experiments. TP level and ALP activity were altered among different treatments. Moderate improvement in mucus secretion was recorded for F1 and F2 treatments than the reference drug. The present results were confirmed by the histopathology findings. Collectively, the current study confirmed the better therapeutic action of formulae 1 and 2 over the pure drug and that F1 was the most potent formula. Also, it encouraged the use of F2 as a curative agent of ulceration rather than a protective one
RESUMEN
Oxidative stress and DNA damage have been implicated in the pathogenesis of many diseases such as chronic inflammation and sepsis. Oxidative DNA damage is an inevitable consequence of cellular metabolism, with a propensity for increased levels following toxic insult. Antioxidants could be a part of a protective strategy to minimize oxidative damage in such cases. The major goal of this study was to examine the ability of two antioxidants namely, alpha lipoic acid [ALA] and Antox [drug preparation] to protect brain from oxidative stress and modify lymphocyte DNA damage induced by lipopolysaccharid [LPS, endotoxin] Randomized seventy-five healthy adult male rats weighing 150-170 g were instructed to our experimental design. Lymphocyte DNA damage was measured using a single-cell gel electrophoresis [comet] assay. LPS injection resulted in a significant alteration on brain oxidative status observed as elevation in the level of malondialdehyde [MDA, index of lipid peroxidation], nitric oxide [NO] and reduction of reduced glutathione [GSH]. Also, the activities of antioxidant defense system, superoxide dismutase [SOD] and cataiase [CAT] were decreased significantly in rats' brain. Moreover, increase in the percentage damage of lymphocyte DNA concentration accompanied with higher tail length was observed following LPS administration. Antioxidants supplementation ameliorated brain oxidative stress by reducing levels of MDA and NO, restoring normal GSH content and normalizing the activities of antioxidant enzymes SOD and CAT. As well as the treated doses lowering the percentage of lymphocyte DNA damage and decreased tail length. In conclusion, antioxidants supplementation by ALA and Antox decreased brain oxidative stress markers and attenuated DNA damage