Zinc supplementation alleviates diabetic peripheral neuropathy by inhibiting oxidative stress and upregulating metallothionein in peripheral nerves of diabetic rats.

We investigated the effect of zinc supplementation on the expression of metallothionein, lipid peroxidation (malondialdehyde, MDA), and poly(ADP-ribose) polymerase-1 (PARP-1) in the sciatic nerve, motor nerve conduction velocity of the left sciatic posterior tibial nerve in streptozotocin (STZ)-induced diabetic rats. Twenty-four male rats were equally divided into four groups. The first group served as untreated controls although the second group received 5 mg/kg/day zinc chloride. The third group was treated with STZ to induce diabetes, and the fourth group was treated with STZ and supplemented with zinc. A gradual but insignificant decline in motor nerve conduction velocity was observed at 2 weeks of induction of diabetes. Zinc supplementation markedly attenuated the decrease in motor nerve conduction velocity at week 8 post-induction of diabetes. Furthermore, the tactile response threshold of diabetic rats receiving normal saline was lower than that of diabetic rats receiving zinc supplementation. Additionally, zinc supplementation accentuated the increase in the mRNA transcript levels of metallothionein but attenuated the increase in the mRNA transcript levels of PARP-1. At week 8 post-induction of diabetes, diabetic rats receiving normal saline had markedly higher MDA contents than diabetic rats receiving zinc supplementation. In conclusion, the present study shows that zinc has a protective effect against diabetes-induced peripheral nerve damage by stimulating metallothionein synthesis and downregulating oxidative stress.