Histopathological and Hematological Effects of Nano-Piperine in Ameliorating Dexamethasone-Induced Immunosuppression in Male Rats

BACKGROUND: Dexamethasone, a potent glucocorticoid, induces immunosuppression. In contrast, nano-piperine enhances the form of piperine through nanotechnology, along with vitamin C, and exhibits immunomodulatory and antioxidant effects. The potential synergy of these compounds in alleviating immune suppression caused by dexamethasone is yet to be fully investigated. OBJECTIVE: This study aimed to assess the histopathological, hematological, and immunomodulatory effects of nano-piperine/vitamin C on immune function in dexamethasone-treated male albino rats. MATERIALS AND METHODS: Forty-eight male Wistar rats (150 ± 10 g, 90-day-old) were adapted to the environment and divided into six groups (n = 8/group). The drugs were administered orally for 30 days continuously. Control (C): Distilled water (0.5 mL). T1: Nano-piperine (15 mg/kg BW). T2: Vitamin C (25 mg/kg BW). T3: Dexamethasone (2 mg/kg BW). T4: Dexamethasone combined with nano-piperine. T5: Vitamin C in addition to dexamethasone. RESULTS: Nano-piperine and vitamin C significantly increased white blood cell (WBC) counts (by 47% and 26%, respectively), lymphocytes, and monocytes (P < 0.05) compared to the control group. Dexamethasone treatment resulted in a significant decrease in WBCs (by 37%), lymphocytes, and monocytes, with a corresponding increase in neutrophils. Co-administration of nano-piperine or vitamin C with dexamethasone partially reversed these effects, leading to a significant increase in WBCs (by 68% and 44%, respectively) compared to the dexamethasone-only group. Serum interleukin-6 (IL-6) and immunoglobulin (IgG, IgA, IgM) levels were significantly reduced in all treatment groups compared to the control group (P < 0.05). Histopathological analysis indicated significant lymphoid degeneration in the dexamethasone-treated group, which was characterized by the absence of germinal centers, vascular congestion, and vacuolated lymphocytes. In contrast, the groups co-treated with nano-piperine or vitamin C showed preserved tissue architecture and reduced damage, supported by semi-quantitative scoring. CONCLUSION: Nano-piperine and vitamin C mitigated dexamethasone-induced immunosuppression by increasing WBC counts, modulating leukocyte differentiation, reducing inflammation (IL-6), and maintaining the integrity of lymphoid tissue. These compounds demonstrate potential as supplementary treatments to reduce immune toxicity associated with glucocorticoids.