Effect of 1,25-(OH)2D3 on pathophysiology of heart, aorta and lungs in male albino rats exposed to chromium(VI)

Abstract

ABSTRACT Introduction: Exposure to heavy metal Cr(VI) causes generation of free radicals, induction of oxidative and nitrosative stress with depletion of antioxidants leading to sequels of cell injury. Fat-soluble 1,25(OH)2D3 is an anti-oxidant capable of reducing noxious effects of oxidative and nitrosative stress caused by Cr-induced generation of reactive oxygen and nitrogen free radicles. Objective: The present study was aimed to evaluate potential role of 1,25(OH)2D3 as an antioxidant against Cr(VI)-induced toxicities in the heart, aorta and lung of experimental animals. Methods: The experimental animals consisted of twenty-four laboratory bred adult male Wistar strain of albino rats, weighing between 180 to 220 grams, which were randomly sorted into four equal groups; each with six rats. Group-1 served as a control with no interventions. Group-2 was exposed to K2Cr2O7 intraperitoneally in a dose of 0.5 mg/kg body weight on alternative days. Group-3 was supplemented with 1,25(OH)2D3 orally in a dose of 12.5 µg/kg daily. Group-4 was given combined K2Cr2O7 and 1,25(OH)2D3 simultaneously with respective doses and routes. The intervention was carried for 21 days. Gravimetry (body weight) and cardiac electrophysiologic analysis (ECG, MAP and HRV) was done pre (Day-1) and post (Day-21) -interventions. During the course of intervention blood sugar was estimated on day-1, 7, 14 & 21. After 21-days of interventions, rats were fasted for 10 hours during the night. Collection of blood samples followed by sacrifice of the rats and collections of tissue specimens of heart, aorta, lungs and liver was carried out on day 22. Results: After 21 days of individual treatments, statistically significant impairments were observed. The Group-2 (K2Cr2O7-exposed) had a significant impairment in; gravimetry (loss of body weight and increased organosomatic index), cardiac autonomic functions (increased sympathetic and decreased parasympathetic causing [1] vasovagal imbalance), hemodynamic (increased HR, MAP, altered HRV) hematologic (reduced Hb, red cell indices, Plt, and increased TLC), glucose homeostasis (increased FBG, OGTT, decreased plasma insulin, increased insulinogenic index and decreased liver glycogen), lipid profile (decreased TC, TGL, LDL and decreased HDL), LFT (increased serum- bilirubin, SGOT, SGPT, ALP, decreased protein and albumin), serum oxidative stress (increased serum MDA), tissue oxidative stress (increased tissue LPO in heart, aorta and lungs), nitrosative stress (increased serum NO), antioxidative markers (deceased SOD, vitamin- C, D & E), molecular marker (increased serum VEGF), chromium (increased serum chromium), histopathogic (morphologic tissue remodeling of heart, aorta and lung tissues) and NWI (increased in coronary arteries and aorta). Supplementation of 1,25(OH)2D3 ameliorated the respective parameters. Conclusion: The results clearly substantiate that chromium-toxicity enhanced the generation of ROS and NOS, causing oxidative and nitrosative stress and affecting pathophysiologic changes in cardiovascular and pulmonary system in male albino rats. It was manifested with cardiac sympathetic over activity and parasympathetic under drive, vasovagal imbalance, hypertension, impaired glucose homeostasis, metabolic, oxidative and nitrosative stress synchronously deprivation of antioxidants, up regulation of vascular functions and tissue remodeling. Supplementation of 1,25(OH)2D3 brought ameliorating reduction in sympathetic over-activity; MAP; metabolic, oxidative and nitrosative stress, cardiovascular and pulmonary remodeling. These effects of 1,25(OH)2D3 could be attributed to its antioxidant property which can possibly be explored as an adjuvant in therapy against Cr(VI) induced toxicity in humans.