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Hepatoprotective Effects of a Ruthenium(II) Schiff Base Complex in Rats with Diet-Induced Prediabetes.

ABSTRACT: Background:Progressive insulin resistance in a prediabetic state has been reported to be the predominant causative factor for the development of nonalcoholic fatty liver disease. The combination of dietary modification and pharmacotherapy has been recommended to manage diabetic liver complications. However, poor patient compliance and toxicity of current drug therapy on liver function still results; thus, newer alternative drugs are required. Objective:This study sought to investigate the hepatoprotective effects of the ruthenium(II) Schiff base complex in the presence and absence of dietary intervention in a diet-induced pre-diabetic rat model. Methods:Prediabetic rats were randomly allocated to respective treatment groups. The ruthenium-based compound (15 mg/kg) was administered to the prediabetic rats in both the presence and absence of dietary intervention once a day every third day for 12 weeks. Results:The administration of the ruthenium compound in both the presence and absence of dietary intervention resulted in the restoration of liver and body weights. This treatment also reduced liver damage enzyme biomarkers, bilirubin, and sterol regulatory element binding protein 1c concentrations in the plasma. Conclusions:The ruthenium(II) complex showed beneficial effects as it ameliorated and prevented the progression of diabetes-related liver derangements while eliminating the hepatotoxicity associated with the use of metal compounds. However, further studies are still required to further determine the physiological mechanisms behind this effect.

SUBMITTER: Mabuza LP

PROVIDER: S-EPMC6911857 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Hepatoprotective Effects of a Ruthenium(II) Schiff Base Complex in Rats with Diet-Induced Prediabetes.

Mabuza Lindokuhle Patience LP Gamede Mlindeli Wilkinson MW Maikoo Sanam S Booysen Irvin Noel IN Nguban Phikelelani Siphosethu PS Khathi Andile A

Current therapeutic research, clinical and experimental 20191113

<h4>Background</h4>Progressive insulin resistance in a prediabetic state has been reported to be the predominant causative factor for the development of nonalcoholic fatty liver disease. The combination of dietary modification and pharmacotherapy has been recommended to manage diabetic liver complications. However, poor patient compliance and toxicity of current drug therapy on liver function still results; thus, newer alternative drugs are required.<h4>Objective</h4>This study sought to investi ...[more]

PMID: 31871510

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Project description:BackgroundBased on the potential of Schiff base compounds to act as sources for the development of cancer chemotherapeutic agents, this in vivo study was performed to investigate the inhibitory properties of the synthetic Schiff base compound Cu(BrHAP)2 on colonic aberrant crypt foci (ACF).MethodologyThis study involved five groups of male rats. The negative control group was injected with normal saline once a week for 2 weeks and fed 10% Tween 20 for 10 weeks, the cancer control group was subcutaneously injected with 15 mg/kg azoxymethane once per week for two consecutive weeks, the positive control group was injected with 15 mg/kg azoxymethane once per week for two consecutive weeks and 35 mg/kg 5-fluorouracil (injected intra-peritoneally) for 4 weeks, and the experimental groups were first injected with 15 mg/kg azoxymethane once per week for two consecutive weeks and then fed 2.5 or 5 mg/kg of the Schiff base compound once a day for 10 weeks. Application of the Schiff base compound suppressed total colonic ACF formation by up to 72% to 74% (P<0.05) when compared with the cancer control group. Analysis of colorectal specimens revealed that treatments with the Schiff base compound decreased the mean crypt scores in azoxymethane-treated rats. Significant elevations of superoxide dismutase, glutathione peroxidase and catalase activities and a reduction in the level of malondialdehyde were also observed. Histologically, all treatment groups exhibited significant decreases in dysplasia compared to the cancer control group (P<0.05). Immunohistochemical staining demonstrated down-regulation of the PCNA protein. Comparative western blot analysis revealed that COX-2 and Bcl2 were up-regulated and Bax was down-regulated compared with the AOM control group.ConclusionThe current study demonstrated that the Cu(BrHAP)2 compound has promising chemoprotective activities that are evidenced by significant decreases in the numbers of ACFs in azoxymethane-induced colon cancer.

Dataset Information

Hepatoprotective Effects of a Ruthenium(II) Schiff Base Complex in Rats with Diet-Induced Prediabetes.

Publications

Hepatoprotective Effects of a Ruthenium(II) Schiff Base Complex in Rats with Diet-Induced Prediabetes.

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