Chronic toxicity and modulatory effects of Deprungsith formulation in Wistar Albino rats.

Abstract

Objectives: Psoriasis is a systematic skin disease. Treatment choice is limited due to unsatisfactory clinical efficacy. The study evaluated the safety of Deprungsith formulation following long-term administration (chronic toxicity test) and its potential modulatory effect on hepatic cytochrome P450 (CYP) enzymes in rats.

Methods: Wistar rats were randomly grouped to receive Deprungsith (125, 500, and 1,000 mg/kg/day) and the satellite (1,000 mg/kg bw) to observe reversibility, as well as distilled water (untreated control) for 9 months. The sentinel-1 group was for environmental risk assessment after 6 months, and the sentinel-2 group was for environmental risk assessment after 9 months). Clinical and behavioral signs, mortality, and histopathology were monitored.

Results: The chronic toxicity study of Deprungsith revealed no evidence of mortality or serious clinical signs at any dosage level. However, changes in WBC count, serum albumin, and sodium, were observed. Histopathological examination identified mild to moderate liver necrosis and renal interstitial inflammation. Low-dose (125 mg/kg bw) significantly induced CYP1A2 and CYP3A1, while high-dose (1,000 mg/kg bw) inhibited CYP1A2 and CYP3A1 activities.

Conclusions: Deprungsith formulation was well-tolerated with an MTD (maximum tolerated dose) and NOAEL (no-observed-adverse-effect level) of 1,000 mg/kg bw. Long-term use of Deprungsith formulation in psoriasis patients should be carefully monitored for therapeutic outcomes (side effects from accumulated levels or unsatisfactory efficacy from inadequate CYP1A2 and CYP3A1-mediated metabolism) and potential herb-drug interactions.