Chronic Oral Epigallocatechin-gallate Alleviates Streptozotocin-induced Diabetic Neuropathic Hyperalgesia in Rat: Involvement of Oxidative Stress

Abstract

Due to the anti-diabetic and antioxidant activity of green tea epigallocatechin-gallate (EGCG), this research study was conducted to evaluate, for the first time, the efficacy of chronic treatment of EGCG on alleviation of hyperalgesia in streptozotocin-diabetic (STZ-diabetic) rats. Male Wistar rats were divided into control, diabetic, EGCG-treated-control and diabetic and sodium salicylate (SS)-treated control and diabetic groups. For induction of diabetes, STZ was intraperitoneally injected (IP) at a single dose of 60 mg/Kg. EGCG was orally administered daily at doses of 20 and 40 mg/Kg for seven weeks; one week after diabetes induction. Finally, hyperalgesia was assessed using standard formalin, hot tail immersion and paw pressure tests. Meanwhile, markers of oxidative stress in brain were measured. Diabetic rats showed a marked chemical, thermal and paw pressure hyperalgesia, indicating that the development of diabetic neuropathy and EGCG treatment at a dose 40 mg/Kg significantly ameliorated the alteration in hyperalgesia (p < 0.05) in diabetic rats as compared with untreated diabetics. EGCG treatment (40 mg/Kg) also significantly decreased diabetes-induced thiobarbituric acid reactive substances formation (p < 0.05) and nitrite (p < 0.05) content and reversed the reduction of antioxidant defensive enzyme superoxide dismutase (p < 0.05). The results may suggest therapeutic potential of EGCG for the treatment of diabetic hyperalgesia through the attenuation of oxidative stress.

Keywords: Diabetic rat; Epigallocatechin-3-gallate; hyperalgesia; oxidative stress.

Figure 1

Body weight in different weeks (mean ± SEM). *: p < 0.05, **: p < 0.001 (as compared with week 0 in the same group); #: p < 0.05 (as compared with diabetics in the same week).

Figure 2

Serum glucose concentration in different weeks (mean ± SEM). *: p < 0.005; **: p < 0.001; ***: p < 0.0001 (as compared with week 0 in the same group); #: p < 0.05; ## p < 0.01 (as compared with diabetics in the same week).

Figure 3

The effect of EGCG and sodium salicylate (SS) on nociceptive scores in the first (early) and second (late) phases of the formalin test. All data represent mean ± SEM. *: p < 0.05, **: p < 0.005, ***: p < 0.0001 (as compared with control); #: p < 0.05, ##: p < 0.01, ###: p < 0.005 (as compared with diabetic).

Figure 4

Effect of EGCG treatment on hyperalgesia in hot tail immersion (A) and paw pressure (B) test. All data represent mean ± SEM. *: p < 0.005; **: p < 0.001 (as compared with control); #: p < 0.05 (as compared with diabetic).

Figure 5

Serum MDA concentration in different groups.*: p < 0.001 (as compared with controls); #: p = 0.02 (as compared with diabetics).

Figure 6

Serum nitrite content in different groups. *: p < 0.01 (as compared with controls); #: p < 0.05 (as compared with diabetics).

Figure 7

Erythrocyte superoxide dismutase activity in different groups.*: p = 0.03 (as compared with controls); #: p < 0.05 (as compared with diabetics).