ABSTRACT
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
ABSTRACT
Oxidative stress plays a key role in sepsis induced by endotoxin lipopolysaccharide [LPS] which is known to enhance the formation of reactive oxygen species [ROS]. In this study, biochemical parameters indicative of hepatic injury and oxidative stress were tested in rat liver following LPS challenge, with or without treatment with the antioxidants alpha lipoic acid [ALA] and Antox [antioxidant drug preparation]. Treatment with LPS alone resulted in a significant [P<0.05] alteration in liver oxidative status observed as elevation in alanine and asparate aminotransferase [ALT and AST] activities, malondialdehyde [MAD, index of lipid peroxidation] level and nitric oxide [NO] concentration. Also, activities of reduced glutathione [GSH]. Superoxide dismutase [SOD] and glutathione peroxidase [GSH-Px] were significantly [P<0.05] reduced in LPS-treated group, as compared to control level. Treatment for seven days with either ALA or Antox prior to or after LPS challenge significantly [P<0.05] decrease ALT, AST, MDA and NO levels when compared to LPS alone. On the other hand, administration of ALA and Antoxa prior to or after LPS treatment significantly increases the activities of GSH, SOD and GSH-Px when compared with LPS treated group. These results indicate that either ALA or Antox may serve as a potentially effective prophylactic agents in alleviating LPS- induced oxidative stress. The beneficial pretreatment effects of the antioxidant against oxidative stress in this study may suggest a potential chemopreventive effect of these compounds in septic prevention