Nephroprotective Effect of Ethanolic Psiadia punctulata Leaf Extract on Iohexol-Induced Nephropathy in a Rat Model

Abstract

Background: Psiadia species is a medicinal plant found in Yemen and several African and Asian countries. It belongs to the family Asteraceae, and Psiadia incana, Psiadia punctulata, and Psiadia schweinfurthii are among the most common species in Yemen. Traditionally, P. punctulata has been used to treat fever, malaria, skin infections, pain, renal calculi, and bone injuries. This study aimed to assess the nephroprotective effect of the ethanolic extract of P. punctulata leaf on iohexol-induced nephropathy in a rat model.

Methods: Thirty-five adult male rats (180 ± 20 g) were used in this study. After one-week acclimatization, the rats were randomly divided into five groups (n = 7 per group). Group 1 received normal saline (1 mL/rat, per os [PO]) for 14 days as the normal control. Group 2 received a single dose of iohexol (15 mg/kg, intraperitoneally [IP]) on day 17. Group 3 received N-acetylcysteine (NAC; 150 mg/kg, IP) for 14 days as a reference drug. Groups 4 and 5 received P. punctulata leaf extract (200 and 400 mg/kg, PO, respectively) for 14 days. All groups were exposed to 72 h of dehydration, and all groups except the normal control received furosemide before iohexol administration. Serum and urine samples were analyzed for renal function biomarkers, including serum creatinine, blood urea nitrogen (BUN), potassium, serum total protein (TP), urine volume, urine cre¬at¬inine, inflammatory markers, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), oxidative stress biomarkers, including malondialdehyde (MDA), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD), and histopathological changes. Data were analyzed using analysis of variance followed by Tukey’s multiple-comparison test, with P <0.05 considered statistically significant.

Results: Iohexol administration caused no significant differences in body weight or kidney weight index compared with the other groups. The iohexol group showed significantly elevated renal biomarkers (serum creatinine, BUN, and serum urea), together with significantly decreased urine creatinine and creatinine clearance, compared with the control group. Iohexol also sig¬nificantly increased pro-inflammatory markers (IL-6 and TNF- α) and the oxidative stress marker MDA, whereas antioxidant biomarkers (GPx, SOD, and CAT) significantly decreased. Treatment with NAC and both doses of P. punctulata extract signifi-cantly decreased serum creatinine, BUN, and serum urea compared with the iohexol group and significantly increased urine creatinine, creatinine clearance, and antioxidant biomarkers (GPx, SOD, and CAT). The high dose of P. punctulata (400 mg/kg) showed the strongest protective effect and significantly increased serum TP levels compared with the iohexol group. This dose also significantly increased serum potassium levels compared with NAC and the lower dose of P. punctulata (200 mg/kg). Histo¬pathological findings supported the biochemical results by showing reduced renal tissue damage in the treated groups.

Conclusion: These findings indicate that P. punctulata extract may exert nephroprotective effects against contrast-induced nephropathy (CIN), primarily through antioxidant and anti-inflammatory mechanisms. The rich phenolic and flavonoid content of the extract warrants further preclinical investigation for preventing CIN.