Obesity related alterations in kidney function and plasma cytokines: Impact of sibutramine and diet in male Wistar rats

Uchenna Agu Francis, Uche Elendu Melford, Kelechi Okechukwu Hope, Adolphus Mbah Chikodili, Chinonye Obioha Kennedy, Orji Abali Isaiah, E. Eghosa, Daniel Chukwu Nwachukwu and
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Abstract

Obesity is a global problem due to widespread consumption of high fat diet (HFD) with implications to well-being. This study was to investigate the modulatory effect of sibutramine and normal diet on obesity-induced alteration in kidney functions and adipokines in Wistar rats. Hundred rats were divided into four groups of 25 each and fed with either normal rat chow (NRC) (group I, control group, n=25) or HFD (n=75). Obese rats were subjected to treatment with HFD (group II, Obese + HFD, n=25), Sibutramine and NRC (group III, Obese + Sibutramine + NRC, n=25); and NRC (group IV, Obese + NRC, n=25) for another 12 weeks. Five rats from each group were sacrificed, urine and blood samples collected for baseline values after the acclimatization period. Similarly, at post induction, 4, 8 and 12 weeks urine and blood samples were collected from 5 rats per group for investigations. Induction of obesity significantly (p<0.05) increased mean Lee index, urine albumin, urine albumin:creatinine ratio, serum interleukin (IL)- 1β, IL -6, tumor necrotic factor (TNF)- α, interferon (IFN) - γ, leptin and decreased urine creatinine and serum adiponectin compared to control. Sibutramine treatment and withdrawal of HFD ameliorated these effects. Obesity induced renal impairment by deranging renal and inflammatory biomarkers investigated in this study. These adverse effects on the kidney were mitigated by sibutramine10 mg/kg/day and NRC by resisting the disturbance, thereby showing nephron-protective effect. The combined treatment of sibutramine with NRC reduced progression of kidney disease to a lesser extent than NRC alone suggesting nonsynergistic effect.
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肥胖相关的肾功能和血浆细胞因子的改变:西布曲明和饮食对雄性Wistar大鼠的影响
肥胖是一个全球性的问题,因为高脂肪饮食(HFD)的广泛消费对健康有影响。本研究旨在探讨西布曲明和正常饮食对肥胖诱导的Wistar大鼠肾功能和脂肪因子变化的调节作用。将100只大鼠分为四组,每组25只,用正常大鼠饲料(NRC)(第一组,对照组,n=25)或HFD(n=75)喂养。肥胖大鼠接受HFD(第II组,肥胖+HFD,n=25)、西布曲明和NRC(第III组,肥胖+西布曲明+NRC,n=25)治疗;和NRC(IV组,肥胖+NRC,n=25)再治疗12周。每组处死5只大鼠,在驯化期后收集尿液和血液样本作为基线值。类似地,在诱导后,从每组5只大鼠中收集4、8和12周的尿液和血液样本进行研究。与对照组相比,诱导肥胖显著增加了平均Lee指数、尿白蛋白、尿白蛋白:肌酐比、血清白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α、干扰素(IFN)-γ、瘦素,并降低了尿肌酐和血清脂联素。西布曲明治疗和停用HFD改善了这些效果。本研究通过紊乱肾脏和炎症生物标志物来研究肥胖诱导的肾损伤。西布曲明10mg/kg/天和NRC通过抵抗干扰减轻了这些对肾脏的不良影响,从而显示出肾单位保护作用。西布曲明与NRC的联合治疗在一定程度上比NRC单独治疗减少了肾脏疾病的进展,这表明其具有非雌激素作用。
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