Hypothyroidism protects against free radical damage in ischemic acute renal failure

The effect of hypothyroidism on ischemic acute renal failure was studied in rats. Ten days after throidectomy with parathyroid reimplantation, rats underwent right uninephrectomy followed by occlusion of the left renal artery for 60 min. Plasma creatine was lower in thyroidectomized than control rats 24 hr after ischemia; 1.3 ± 0.5 vs 3.2 ± 0.6 mg%; P < 0.05. Twenty-four hours after ischemia, inulin clearance was higher in thyroidectomized than control animals (0.40 ± 0.06 vs. 0.17 ± 0.03 mliter/min; P < 0.01), despite an initially lower inulin clearance in thyroidectomized animals (0.81 ± 0.08 vs. 1.1 ± 0.07 mliter/min; P < 0.05). Administration of the antithyroid drug prophylthiouracil for 14 days also resulted in lower plasma creatinine after ischemia. Kidneys from thyroidectomized animals showed less histologic damage 24 hr after ischemia. Renal cortical content of the lipid peroxidation product malondialdehyde was increased less in thyroidectomy than control kidneys after 60 min ischemia plus 15 min reflow (0.08 ± 0.02 vs. 0.42 ± 0.1 nmole/mg protein; P < 0.005). Renal cortical glutathione content was higher in thyroidectomized animals by approximately 36%, 650 ± 46 vs. 479 ± 32 nmole/mg protein (P < 0.02). In normal rats, glutathione infusion also increased renal cortical glutathione content and resulted in lower plasma creatinine 24 hr after renal artery ischemia. Therefore, hypothyroidism resulted in functional and histologic protection against injury after ischemia. Post-ischemic renal lipid peroxidation was reduced in thyroidectomized animals, perhaps the result of increased scavenging of reactive oxygen species (oxygen free radicals and H₂O₂) by glutathione.