Alterations in L-Histidine Transport in-Response to Aspirin- and Nimesulide-Induced Toxicity in Rat Intestine Using Everted Intestinal Sacs.

The present study was carried out to investigate the aspirin-and nimesulide-induced alteration in the amino acid L-histidine transport across the intestine. These drugs represent the two groups of nonsteroidal anti-inflammatory drugs (NSAIDs) with varying cyclooxygenase-2 (Cox-2) selectivities and are associated with increased risk of gastrointestinal side effects. Female Wistar rats were divided into three different groups: group I (control), group II (aspirin-treated, 50 mg/kg), and group III (nimesulide-treated, 10 mg/kg). At the end of 28 days of treatment, the jejunal segment was isolated and everted sacs were prepared so as to study the transport properties of L-histidine and its kinetics. A significant decrease in the transport of histidine in both the treatment groups was seen as compared to the control. Changes in Michaelis-Menten parameters viz:-V(max) and the thermodynamic parameter E(a) were also seen. However, K(m) and T(c) remained constant. When studied at different time intervals, both the treatment groups demonstrated an initial rapid transport of L-histidine, which showed saturation at longer durations. Taken together, these results indicate the adverse effects of these two NSAIDs on the intestinal mucosa. Further research, however, is warranted to understand the molecular basis of NSAID-induced GI side effects and to comment decisively on the safety profile of these drugs.