Biochemical Evidence Indicates the Preventive Effect of Resveratrol and Nicotinamide in the Treatment of STZ-induced Diabetic Cataract

ABSTRACT

Purpose

High glucose level is a strong initiator of both oxidative stress and DNA damage to various cellular proteins. This activates the poly ADP-ribose polymerase (PARP) enzyme, which is responsible for disturbing physiological energy metabolic homeostasis. The present study aimed to elucidate the association between stress and the PARP pathway by using resveratrol (RSV) and nicotinamide (NAM, PARP inhibitor) to treat diabetic cataract.

Method

Albino rats were used for the experimental study. A single streptozotocin administration (55 mg/kg, i.p.) prompted diabetes in the animals. The experimental groups were the normal group (non-diabetic) and the diabetic groups: the diabetic control animals (group D), the diabetic animals treated with RSV at 40 mg/kg/day, i.p. (D+ RSV group), NAM at 100 and 300 mg/kg/day, i.p. (D+ NAM100, D+ NAM300 groups, respectively), and a combination of RSV and NAM i.p. (D+ RSV+NAM100 = Combi 1 group, D+ RSV+NAM300 = Combi 2 group). Glucose levels and the eyes were examined biweekly; various cataractogenic parameters in the lenses were examined after completion of the eight-week experimental protocol.

Results

Compared to diabetic control, RSV monotherapy significantly decreased hyperglycemia and other lenticular alterations. NAM at the high dose only showed beneficial effects without altering the blood glucose level, lenticular aldose reductase (AR) activity, and sorbitol content, primarily restored the lenticular NAD level and decreased oxidative stress in diabetic rats. These findings regarding NAM treatment indicate that a pathway other than the antioxidant defense system and the polyol pathway, which might be due to PARP inhibition, is involved in diabetic cataracts. Moreover, compared to RSV monotherapy, combination treatments were effective.

Conclusion

These results indicate that hyperglycemia and oxidative-osmotic-nitrosative stress play central roles in the pathophysiology of diabetic cataracts. Moreover, our study also revealed that concurrent treatment with the RSV and NAM may prove useful in the pharmacotherapy of diabetes and its secondary complications such as cataract.

KEYWORDS:

• Diabetic cataract
• resveratrol
• diabetes
• oxidative stress
• nicotinamide

Animal regulation policy

The experiments were performed in accordance with the regulations specified by the Institutional Animal Ethics Committee (IAEC), Guru Ghasidas Vishwavidyalaya, Bilaspur, India. The guidelines of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA) were strictly followed throughout the experimental protocol.

Acknowledgments

The authors are thankful to Guru Ghasidas Vishwavidyalaya, Bilaspur (C.G.), India, for supporting this study and for providing essential facilities from the UGC-SAP and the AYUSH-EMR projects to carry out this work. Amrita Singh is thankful to the Indian Council of Medical Research (ICMR) for providing her monthly fellowship as a senior research fellow (No. 45/17/18-PHA/Toxi/BMS/OL). The authors also thank Edward J. Button, PhD, and CEO of Button and Associates, Virginia, USA, for reviewing the English in this manuscript.

Disclosure statement

The authors declare that they have no conflicts of interest.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.