Tert-butylhydroquinone Mitigates Renal Dysfunction in Pregnant Diabetic Rats via Attenuation of Oxidative Stress and Modulation of the iNOs/ NFkB/TNF Alpha Signalling Pathway

Abstract

Aim: The aim of the study was to determine the effect of tert-butylhydroquinone (tBHQ) supplementation on some biochemical parameters in pregnant diabetic rats and the foetus.

Background: The global incidence of gestational diabetes mellitus (GDM) has been on the increase despite current interventional therapies, underscoring the need for alternative or complementary therapeutic approaches.

Objective: The objective is to determine the effect of tBHQ on blood glucose, insulin resistance, body weight, relative liver and kidney weights, serum lipid profile (total cholesterol, triacylglycerol, high-density lipoprotein cholesterol and very low-density lipoprotein cholesterol), liver function (albumin, aspartate and alanine amino transaminases) and kidney function markers (urea, creatinine and uric acid) in the sera, and study maternal and foetal renal levels of oxidative stress and inflammatory markers, foetal weights and histology of the kidney of streptozotocin (STZ)-induced GDM in rats.

Methods: Twenty female pregnant rats were used, and they were divided into four groups of control (normal pregnancy), disease (diabetic untreated), metformin (received 200 mg/kg metformin dissolved in distilled water) and tBHQ groups (received 25 mg/kg tBHQ in 1% corn oil), respectively, with five rats in each group. GDM was induced in the disease and treated groups by intraperitoneal injection of STZ (45 mg/kg in sodium citrate buffer, pH 4.5).

Results: STZ induction in the disease group significantly increased their blood glucose levels (P<0.05), altered their body and foetal weights, relative liver and kidney weights, serum lipid profile, liver and kidney function markers in the sera (relative to the control), inducing oxidative stress and inflammation to the maternal and foetal kidneys and altering the maternal kidney histology, which was found to be improved following supplementation with tBHQ in a manner akin to or even better than metformin.

Conclusion: tBHQ was found beneficial in protecting the foetal kidneys against oxidative stress and the foetus against mortality arising from maternal hyperglycaemia. Finally, the study showed the potential of tBHQ in mitigating histological changes in the maternal kidney arising from STZinduced hyperglycemia in rats.

Keywords: Antioxidants; endocrine systems; hyperglycaemia; inflammation; insulin resistance; oxidative stress.