Methimazole-induced hypothyroidism in rats ameliorates oxidative injury in experimental colitis

Abstract

Depression of metabolism by hypothyroidism decreases oxidant production and thus protects tissues against oxidant damage. Moreover, it is well-known that abnormal gut motility is a common manifestation in hypo/ hyperthyroidism. In this study, we aimed to investigate the putative beneficial effects of methimazole on oxidative injury and dysmotility in a rat colitis model. Methimazole (0·04%) was administered in drinking water starting 15 days prior to induction of colitis. Colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid (30 mg/ml; 0·8 ml) in ethanol. Six days after the induction of colitis, the fecal output was measured and used as an index for colonic motility. All rats were decapitated on the seventh day. The distal colon was weighed and the mucosal lesions were scored. Colonic lipid peroxidation (LP) and glutathione (GSH) measurements were performed. The macroscopic score, the colonic wet weight and LP values of the euthyroid colitis group were found to be higher than those of the control group (P<0·05-0·001). All these parameters were reduced in the methimazoletreated colitis group (P<0·01-0·001). The decrease in colonic GSH levels in the colitis group was completely abolished in the methimazole-treated colitis rats (P<0·01). Induction of colitis increased the average fecal output compared with the control group (P<0·05) and methimazole in the colitis group exaggerated the fecal output (P<0·001). In conclusion, methimazole reduces colonic oxidative injury probably due to hypometabolism, which is associated with a decrease in the production of reactive oxygen intermediates and an increase in the response of antioxidant systems.

Regulation of oxidative stress and lipid peroxidation in PTU induced mice, treated with Pyrroloquinoline quinone (PQQ)

“…These observations corroborate with the earlier reports, where free radical scavenging property of PQQ has been highlighted (Misra et al, 2004;Shrivastava et al, 2010).With other two concentrations of PQQ (1 and 5 mg /kg) also, LPO was inhibited in the tissues of all the studied organs, with a significant elevation in SOD and CAT. Some workers suggest that hypothyroidism protects tissues against accelerated lipid peroxidation, although the data concerning oxidation / antioxidation in hypothyroidism are incomplete and contradictory (Isman et al, 2003;Venditti and Di Meo, 2006). In fact, Dariyerli et al, (2004) did not find any change in the content of malondialdehyde in rats with thiamizoleinduced hypothyroidism.…”

Influence of Beta-Endorphin on Oxygen Activity of Neutrophils and Total Antioxidant Status in Rats after Chronic Administration of Methimazole

“…The results concerning TAS revealed that chronic administration of methimazole stimulated protection against free radicals. Such conclusions, based on the previous analyses, have already been presented (16,32), although it is still a matter of debate (26).…”

“…Hypothyroidism lowers tissue oxygen demand and is associated with the decreased production of free oxygen radicals. It also protects tissues against lipid peroxidation, stimulating the mechanisms of the antioxidant system (16,23,35). Methimazole is an anti-thyroid drug commonly used around the world in the long-term treatment of hyperthyroidism in humans (11,15,27,39), dogs (37), and cats (12,13,18,24,25,36).…”

“…It also reduces the activity of myeloperoxidase and probably the NADPH oxidase system in peripheral blood neutrophils, which are a significant source of free oxygen radicals (10,29,31). Although this drug inhibits lipid peroxidation in rats, there are reports stating that the induced hypothyroidism state impairs the pro-oxidative − anti-oxidative balance in this species (16). It has been also presented that hypothyroidism triggered by methimazole damages cells by inducing oxidative stress, but it is not associated with hypothyroidism per se (4,7,8,14,30).…”

Features endogenous intoxication in rats with galactosamined hepatitis on the background of merkazolil-induced hypothyroidism

“…тика мерказолілу ("Здоров'я", Україна) в дозі 25 мг/кг протягом 21-ї доби [14]. Контроль здій-снювали за рівнем тироксину, трийодтироніну і тиреотропного гормону, а також за масою тварин і їх руховою активністю.…”