Antidiabetics in combination with hydroxychloroquine improve antioxidant and hepatoprotective activities in alloxan-induced diabetic rats

Abstract

Hyperglycemia exerts toxic effects on the pancreatic β-cells. This study investigated the hypothesis that the antidiabetic drugs glibenclamide and metformin, in combination with hydroxychloroquine (HCQ) offer additional protection for the pancreas against oxidative stress and produce hepatoprotective effect in alloxan-induced diabetic rats. Diabetes was induced in male Long-Evans rats by a single dose of alloxan (120 mg/kg; i.p.). Different groups of diabetic animals were treated with glibenclamide (10 mg/70 kg, i.p.), metformin (850 mg/70 kg, i.p.), HCQ (300 mg/70 kg, i.p.) and combination of both glibenclamide and metformin with HCQ, separately for a period of 28 days. Diabetic rats had significantly elevated levels of serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT), while catalase (CAT) and superoxide dismutase (SOD) activity were significantly reduced. Glibenclamide and metformin produced no significant effects on antioxidant enzymes but both showed significant (p<0.05) result in reducing SGOT and SGPT level in diabetic rats. In contrast, the combination of glibenclamide or metformin with HCQ showed better effect on up-regulation of CAT and SOD activity and down-regulation of SGOT and SGPT activity in comparison with the antidiabetic drug alone. These findings suggest that, HCQ potentiates the effect of glibenclamide and metformin to protect pancreas against oxidative stress and produce hepatoprotective effect in diabetic rats.

Beneficial Effects of Combination Therapy of Sitagliptin and β-carotene Drugs on Streptozotocin-induced Diabetic Rats

“…The enzymes SGPT, a cytosolic enzyme primarily present in the liver and SGOT, a mitochondrial enzyme released from heart, liver, skeletal muscle and kidney are the most sensitive markers employed in the diagnosis of liver diseases. These enzymes leak through the liver cell membrane into the blood circulation while liver cells are injured or died, and serum levels become increase (Zannah et al, 2015). It is concluded that diabetes is associated with hepatocellular damage (Thenmohzi and Subramanian, 2009) as diabetic rats show a significant increase of these markers.…”

Synergistic Effect of β-Carotene and Metformin on Antihyperglycemic and Antidyslipidemic Activities in Streptozotocin-Induced Diabetic Rats

“…Group C Diabetic rats treated with metformin (daily administered 850 mg/70 kg b.w.) [18]. Group D Diabetic rats treated with β-carotene (daily administered 10 mg/70 kg b.w.)…”

Combination Therapy of Momordica charantia Linn. (Bitter Melon) with Antihyperglycemic Agent Gives Increased Antioxidative and Hepatoprotective Actions in Alloxan-induced Diabetic Rats

“…The present long term studies on the combination therapy of BME with metformin provided some light on the beneficial effects like antioxidant and hepatoprotective actions in normal and AIDRs. IP injection of freshly prepared alloxan monohydrate (110 mg/kg BW) solution was used to induce diabetes (BGL ≥ 11.1 mmol/l) among the 16 hours fasted rats (Zannah et al, 2015). Alloxan selectively kills the pancreatic -cells because it preferentially accumulates in cells through uptake via the GLUT2 glucose transporter.…”

“…Both of these enzymes are the most sensitive markers employed in the diagnosis of liver diseases. When liver cells are injured or died, these enzymes can leak through the liver cell membrane into the blood circulation and serum levels become increase (Zannah et al, 2015). As diabetic rats show a significant increase in these liver markers so it is conclusive that diabetes is associated with hepatocellular damage (Thenmohzi and Subramanian, 2009).…”