Mangiferin protects the streptozotocin-induced oxidative damage to cardiac and renal tissues in rats

doi:10.1016/S0300-483X(02)00069-0

Toxicology

Volume 176, Issue 3, 15 July 2002, Pages 165-173

https://doi.org/10.1016/S0300-483X(02)00069-0 Get rights and content

Abstract

The role of oxidative stress in streptozotocin (STZ)-induced toxicity and its prevention by a xanthone glucoside, mangiferin was investigated. To induce diabetes mellitus, adult male Wistar rats were injected STZ intravenously at 55 mg/kg body weight. The effect of mangiferin (10 and 20 mg/kg, i.p., 28 days) was investigated in STZ-induced diabetic male rats. Insulin-treated rats (6 U/kg, i.p., 28 days) served as positive control. Diabetic rats given normal saline served as negative control. Normal rats that neither received STZ nor drugs served as normal control. On day 28, the diabetic rats showed significant increase in serum creatine phosphokinase (CPK) and total glycosylated haemoglobin. Kidney revealed tubular degeneration and decreased levels of superoxide dismutase (SOD) and catalase (CAT) with an elevation of malonaldehyde (MDA). Cardiac SOD, CAT and lipid peroxidation were significantly increased. Histopathological findings revealed cardiac hypertrophy with haemorrhages. Analysis of erythrocyte revealed significantly elevated levels of MDA with insignificant decrease in CAT and SOD. Repeated intraperitoneal injections of mangiferin (10 and 20 mg/kg) and insulin (6 U/kg) controlled STZ-induced lipid peroxidation and significantly protected the animals against cardiac as well as renal damage. From the study, it may be concluded that oxidative stress appears to play a major role in STZ-induced cardiac and renal toxicity as is evident from significant inhibition of antioxidant defence mechanism in renal tissue or a compensatory increase in antioxidant defence mechanism in cardiac tissue. Intraperitoneal administration of mangiferin exhibited significant decrease in glycosylated haemoglobin and CPK levels along with the amelioration of oxidative stress that was comparable to insulin treatment.

Introduction

Mangiferin, a recently known pharmacologically-active phytochemical, is present in different plants, including Mangifera indica L. Its chemical name is 2-C-β-d-gluco-pyranosyl-1,3,6,7-tetrahydroxyxanthone, molecular formula: C₁₉H₁₈O₁₁, molecular weight: 422.35, melting point: anhydrous 271 °C. Some important pharmacological activities of mangiferin have been reported as antitumor (Guha et al., 1996) and antiviral (Zheng and Lu, 1990, Zbu et al., 1993, Guha et al., 1996, Yoosook et al., 2000). Recently, pharmacological functions of mangiferin in altering the oxidative mechanisms have received much attention (Sanchez et al., 2000). It has also been found to be effective in non-insulin dependent diabetes mellitus (Ichiki et al., 1998).

It has been well documented that diabetes mellitus is associated with generation of reactive oxygen species (ROS) leading to oxidative damage particularly to heart and kidney (Mohamed et al., 1999). The elevated blood glucose levels in diabetes mellitus are thought to induce cell death through free radical formation that occurs as a common sequelae to diabetes-induced non-enzymatic modification of sugar moieties on proteins and lipids (Donnini et al., 1996). It is, therefore, thought worthwhile to investigate the protective role of mangiferin against cardiac and renal oxidative injury induced by streptozotocin (STZ) toxicity in insulin-dependent diabetic rats.

Section snippets

Chemicals

STZ, reference mangiferin and 3-(4,5-dimethyl thiazole-2yl) 2,5-diphenyl tetrazolium bromide (MTT) were purchased from M/s Sigma Chemicals, USA. Acetic acid and acetonitrile of HPLC grade were procured from M/s E. Merck (India) Ltd. India. All the solvents used in the study were of analytical grade.

Preparation of mangiferin

Mangiferin was isolated from M. indica leaves by the method of Ghosal and Rao (1996) with slight modification. Shade-dried and powdered leaves of M. indica was soxhleted for 12 h with petroleum ether

Antidiabetic activity of mangiferin

Whole blood glycosylated haemoglobin levels were found to be significantly elevated in STZ-induced diabetic rats as compared to normal rats (Table 1). Treatment with insulin (6 U/kg, i.p.) resulted in a significant (P<0.01) reduction in the levels of glycosylated haemoglobin as compred to negative control. Mangiferin (10 and 20 mg/kg, i.p.) also exhibited a significant (P<0.05) antidiabetic activity as compared to negative control (Table 1). However, the glycosylated haemoglobin levels were not

Discussion

STZ is a commonly employed compound for induction of diabetes mellitus in experimental rats (Tomlinson et al., 1992). Recently, it has been reported that long standing hyperglycaemia with diabetes mellitus leads to the formation of advanced glycosylated end products which are involved in the generation of ROS, suggesting the mechanism by which hyperglycaemia causes oxidative damage (Mohamed et al., 1999). Thus, it is worthwhile to study the lipid peroxidation in long standing cases of diabetes

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Toxicology

Abstract

Introduction

Section snippets

Chemicals

Preparation of mangiferin

Antidiabetic activity of mangiferin

Discussion

References (18)

Glucose may induce cell death through a free radical-mediated mechanism

Biochem. Biophys. Res. Commun.

High-performance liquid chromatographic method for the determination of mangiferin, likviritin and dihydroquercetin in rat plasma and urine

J. Chromatogr.

Protein measurement with folin-phenol reagent

J. Biol. Chem.

Assay for lipid peroxides in animal tissues by Thiobarbituric acid reaction

Anal. Biochem.

Protective effects of Mangifera indica L. extract, mangiferin and selected antioxidants against TPA-induced biomolecules oxidation and peritoneal macrophage activation in mice

Pharmacol. Res.

Anti-herpes simplex virus activities of crude water extracts of Thai medicinal plants

Phytomedicine

A plausible chemical mechanism of bioactivities of mangiferin

Indian J. Chem.

Antitumor, immunomodulatory and anti-HIV effect of mangiferin, a naturally occurring glucosylxanthone

Chemotherapy

New antidiabetic compounds, mangiferin and its glucoside

Biol. Pharm. Bull.

Cited by (195)

Room temperature intercalated poly(diallyldimethylammonium chloride)@montmorillonite as an ultrasensitive mangiferin electrochemical sensor component

The intracellular fate and transport mechanism of shape, size and rigidity varied nanocarriers for understanding their oral delivery efficiency

The role of inflammation in cadmium nephrotoxicity: NF-κB comes into view

Bioactivity, benefits, and safety of traditional and ethnic foods

Sinapic acid ameliorates cardiac dysfunction and cardiomyopathy by modulating NF-κB and Nrf2/HO-1 signaling pathways in streptozocin induced diabetic rats

Therapeutic potential of mangiferin in the treatment of various neuropsychiatric and neurodegenerative disorders