Chloroquine was once thought to be a promising treatment for
COVID-19 but it quickly failed due to its inefficiency and association with increased mortality. Further, comorbidities such as
hypertension may have contributed this failure. The safety and toxicity of
chloroquine at doses required for treating
SARS-CoV-2 infection in hypertensive patients remain unknown. Herein, to investigate these effects, we performed a safety evaluation of
chloroquine at the approved dose (63 mg/kg) and at a high dose (126 mg/kg) in hypertensive rats. We found that
chloroquine increased the mortality of hypertensive rats to 18.2% and 100%, respectively, after 7 days. During the
chloroquine exposure period, the bodyweight, feed, and water consumption of hypertensive rats were decreased significantly. In addition, we show that
chloroquine induces prolongation of QTc interval, elevation of LDH and CK, and histopathological damage of the myocardium in hypertensive rats.
Ocular toxicity was observed in hypertensive rats in the form of
hemorrhage in the eyes and
retinal damage. Furthermore, we also observed intestinal toxicity in hypertensive rats, which presented as thinning intestinal walls with hemorrhagic contents, and histopathological changes of the jejunum. Hepatotoxicity was also evidenced by elevated ALT, and vacuolization of hepatocytes was also observed. Nephrotoxicity was observed only in high dose
chloroquine-treated hypertensive rats, presenting as alterations of urinalysis and renal function. Immune alterations were also found in high-dose
chloroquine-treated hypertensive rats with elevation of serum
IL-10, IL-1β and GRO, and moderate damage to the spleen. In summary, this study partially explains the reason for the failure of
chloroquine as a
COVID-19 therapy, and underlines the importance of safety evaluation and medical supervision of
chloroquine to avoid patient harm, especially to those with
hypertension.