Volume 16, Issue 38, July - December, 2022

Effect of the 5-alpha-reductase inhibitor finasteride on experimentally-induced pain, inflammation, gastric lesions and liver injury

Abdel-Salam OME^1♦, Sleem AA², Omara EA³

¹Department of Toxicology and Narcotics, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt
²Department of Pharmacology, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt
³Department of Pathology, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt

^♦Corresponding author
Department of Toxicology and Narcotics, Medical Research and Clinical Studies Institute, National Research Centre, Dokki, Cairo, Egypt

ABSTRACT

Finasteride, a 5-alpha-reductase inhibitor, used in treatment of benign prostatic hypertrophy was evaluated in acute nociceptive pain models of thermal, chemogenic and visceral inflammatory pain, carrageenan-induced paw oedema, Porsolt’s forced swimming test and Morri’s water maze test in mice. Finasteride was also tested in the indomethacin-induced gastric mucosal damage and in acute liver injury caused by carbon tetrachloride (CCl4) in the rat. Finasteride given intraperitoneally (i.p.) 1h beforehand at doses of 0.25-2 mg/kg significantly increased the response latency in the mouse hot plate test. The drug given orally (0.5-2 mg/kg) or intraperitoneally (i.p.) (0.25-1 mg/kg) caused significant dose-dependent antinociceptive effect in the mouse acetic-acid-induced writhing assay. The co-administration of finastertide (2 mg/kg, i.p.) with either ketoprofen or celecoxib resulted in increased analgesic effect. The drug given at 0.5-1 mg/kg, i.p. reduced the duration of paw licking induced by intradermal capsaicin injection. Finasteride (0.5- 1 mg/kg, i.p.) inhibited the paw oedema response to subplanter carrageenan injection in a dose-dependent manner. Finasteride (0.125-1 mg/kg, i.p.) did not alter immobility time in the Porsolt’s forced swimming test. The drug (1 or 2 mg/kg, i.p.) had no significant effect on the antidepressant activity of fluoxetine but increased that of imipramine. The latency to locate the submerged platform in the MWM test was not affected by the administration of finasteride. The drug (2 mg/kg, i.p.) increased gastric mucosal lesions caused by indomethacin. Finasteride at 1 or 2 mg/kg showed no significant effect on CCl4-induced increase in serum liver enzymes but the drug at 2 mg/kg reduced the silymarin-induced liver protection. In conclusion, finasteride displayed antinociceptive and anti-inflammatory activities. It does not appear to have depressant-like properties or impair short-term working memory at the doses employed in the present study. The drug may increase gastric lesions due to non-steroidal anti-inflammatory agents and cause liver damage.

Keywords: finasteride, visceral pain, thermal pain, antidepressant activity, gastric ulcer

Drug Discovery, 2022, 16(38), 110-123

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