Effect of the antioxidant α-tocopherol in an experimental model of pulmonary hypertension and fibrosis: Administration of monocrotaline

Monocrotaline, a pyrrolizidine alkaloid, causes in mammals a respiratory condition closely resembling adult respiratory distress syndrome and chronic obstructive pulmonary disease, which is preceded in the lung parenchyma by high levels of angiotensin converting enzyme and angiotensin II. Vitamin E (α-tocopherol) is a powerful antioxidant that is beneficial in the treatment of several acute and chronic pulmonary injuries by inhibiting the vasoconstrictive and mitogenic activity of angiotensin II. We report the effects of dietary vitamin E supplementation on monocrotaline-induced injury in the rat. Vitamin E was effective in moderating the inflammatory injury at a dose of 1667 mg/kg diet, although pulmonary vasculitis persisted. A vitamin E dose of 3333 mg/kg diet resulted in pulmonary and hepatic hemorrhage; a monocrotaline mitigating effect could not be demonstrated as well as with the lower dose because of this pathology, especially in the liver. Further study is recommended to determine the minimum effective dose of vitamin E that does not cause hemorrhage.