Possible role of l-carnitine in improvement of metabolic and hepatic changes in hyperuricemic and hyperuricemic-Fructose-supplemented rats.

Hyperuricemia was linked to diabetes mellitus, metabolic syndrome, and oxidative stress, and could be induced by higher fructose consumption through altering energy status in liver. l-Carnitine is an antioxidant, affecting mitochondria and cellular energetics; however, little is known about its effects in hyperuricemic states. This study investigated metabolic and hepatic effects of hyperuricemia and fructose feeding, and demonstrated the role of l-Carnitine in such states. Fifty adult male Wistar rats were randomly divided into control, untreated hyperuricemic, fructose-supplemented hyperuricemic, l-Carnitine-treated hyperuricemic, and l-Carnitine-treated fructose-supplemented hyperuricemic groups. The separated plasma was used for determination of the glycemic control, lipid profile, liver function tests, uric acid level, and oxidative stress markers. Atherogenic index, HOMA-IR, and body mass index (BMI) were calculated. Left liver lobe and left kidney specimen from all groups were used for histopathological studies. Hyperuricemic rats exhibited significantly hypoalbuminemia, dyslipidemia, insulin resistance, and oxidative stress compared to the controls. Fructose-supplemented hyperuricemic group showed obesity and more deleterious effects, as well as, steatosis, and renal tubular damage compared to the hyperuricemic rats. Concomitant l-Carnitine treatment with hyperuricemia improved such effects, despite causing adiposity. While combined l-Carnitine treatment and fructose supplementation in hyperuricemia limited the aggressive hyperuricemic picture of fructose supplementation. It is concluded that hyperuricemia has detrimental metabolic and hepatic effects. Artificial fructose supplementation worsened such effects, while l-Carnitine was efficient in ameliorating these hyperuricemia and/or excess fructose-induced hyperuricemia effects, through its anti-inflammatory, antisteatotic, and antioxidant properties.

Lipopolysaccharide repeated challenge followed by chronic mild stress protocol introduces a combined model of depression in rats: reversibility by imipramine and pentoxifylline.

OBJECTIVES: The present study examined the effect of combined exposure to repeated challenge using low doses of lipopolysaccharide (LPS) and chronic mild stress (CMS) together. This combined exposure is thought to expose the animals to more realistic challenges, testable on different levels (behavioral, neurochemical, immunohistochemical and gene expression). The role of glial cells was examined, as well. Additionally, the effects of chronic administration of the tricyclic antidepressant imipramine and the anti-TNF-α pentoxyphylline were investigated. METHODS: Wistar rats were exposed to either repeated LPS (50µg/kg i.p.) over 2weeks, CMS protocol for 4weeks or LPS over 2weeks then 4weeks of CMS. Two groups of rats were exposed to LPS/CMS protocol and treated with either imipramine or pentoxifylline. Rats were examined for behavioral, neurochemical and gene expression changes. RESULTS: Animals exposed to LPS/CMS elaborated depressive-like symptoms with significant increase in both serum corticosterone and TNF-α levels compared to those in the saline, LPS or CMS groups. Hippocampal kynurenine/tryptophan ratio and TNF-α gene expression showed significant increase in the LPS/CMS model compared to those in saline, LPS or CMS groups. The immunohistochemical findings scrutinized the topography of the examined effects. Chronic treatment with imipramine or pentoxifylline significantly ameliorated the behavioral, neurochemical, immunohistochemical and TNF-α gene expression changes induced by the LPS/CMS protocol. CONCLUSION: This study gave a clue to the neurobiological processes underlying, at least, the subtypes of depressive disorders. It highlighted the possible interactions between stress and immune-inflammatory pathways in the pathogenesis of depression and suggested a new animal model of depression that addresses these pathways.