Antioxidant Supplementation with ProCloSupp Protects Against Renal Toxicity of Atypical Antipsychotics in Rats: Implications for Safer Treatment Strategies

Atypical antipsychotics (AAP), including clozapine (Clo), aripiprazole (Ari), and risperidone (Ris), are widely used in psychiatry but can lead to kidney damage due to oxidative stress. This study investigated whether dietary supplementation with selected antioxidants-ellagic acid, vitamin C, zinc, and seleno-methionine (SeMet) in fish oil, formulated as the composite product "ProCloSupp" (PCS)-can mitigate the oxidative damage induced by subchronic administration of AAP. Rats were treated with each antipsychotic for 28 days, with PCS added in the last 14 days. The kidney tissue was examined histologically and by determining the activities of antioxidant enzymes (copper, zinc and manganese superoxide dismutase-CuZn SOD and Mn SOD, catalase-CAT, glutathione peroxidase-GPx, glutathione reductase-GR, glutathione S-transferase-GST). All AAPs caused discrete to moderate renal damage and significant changes in enzyme profiles, which were most pronounced with Ari. Clo and Ari significantly decreased CuZn SOD and Mn SOD activity, while Ris only affected Mn SOD. Clo additionally increased CAT activity, while Ari increased GPx activity. Antioxidant-related protein levels increased only in the Ris group. PCS supplementation increased CuZn SOD and GPx activities and was associated with less pronounced histopathological changes than antipsychotic treatment alone. In conclusion, subchronic Clo, Ari, and Ris exposure induces oxidative renal damage in rats, while PCS supplementation enhances antioxidant defences and attenuates tissue damage. These results support PCS as a potential nephroprotective strategy in antipsychotic therapy.