Consequences of Mrp2 deficiency for diclofenac toxicity in the rat intestine ex vivo

Gallic acid mitigates diclofenac-induced liver toxicity by modulating oxidative stress and suppressingIL-1βgene expression in male rats

“…Glutathione (GSH), an endogenous antioxidant, plays a main role in cellular defense in damage caused by oxidative stress. Both in vitro and in vivo reports have implicated the role of GSH depletion in oxidative stress induced by DIC in different model systems (Ahmad et al 2013;Alabi et al 2017;Niu et al 2015). In the present study, DIC-induced liver toxicity caused a remarkable elevation in the GSH content in liver tissues (Table 3) compared to the control group.…”

“… 2017 ; Niu et al. 2015 ). In the present study, DIC-induced liver toxicity caused a remarkable elevation in the GSH content in liver tissues ( Table 3 ) compared to the control group.…”

Silymarin mitigates diclofenac-induced liver toxicity through inhibition of inflammation and oxidative stress in male rats

“…Intracellular glutathione (GSH), the principal endogenous antioxidant, creates a critical role in defense of cell on damage induced by oxidative stress. Both in vivo and in vitro studies have shown the effect of GSH depletion in oxidative stress induced by DIC in various model systems (27,30,34). In our research, DIC-induced liver toxicity led to a noticeable reduction in the content of GSH in liver tissues relative to the control animals.…”

Precision-cut intestinal slices: alternative model for drug transport, metabolism, and toxicology research

“…The biotransformation of diclofenac into the 4ʹ-OH and 5-OH metabolites and acyl glucuronide diclofenac was investigated in rat [73,74] and human PCIS [75] and also showed a higher rate of metabolism in human than in rat tissue. Moreover, the different metabolic routes could be specifically inhibited by specific inhibitors.…”

“…Mdr1a knockout mouse) can be helpful to identify transporters involved in the transport of a drug under study. [74] The sensitive nature of the intestine necessitates to monitor the quality of the intestine and the viability of PCIS using viability markers, for example, the intracellular ATP and morphology, in each experiment and for every compound of interest. Moreover, a further optimization of culture medium would be very useful for maintenance not only of viability but also of DME and DT activity.…”