Effects of ATP and Lacidipine on Atezolizumab-Associated Oral and Gastrointestinal Mucosal Alterations in Rats

Background and Objectives: Atezolizumab-associated oral and gastrointestinal (GI) mucosal alterations may involve oxidative stress and inflammation. This study evaluated oral and GI mucosal outcomes in rats receiving atezolizumab alone or in combination with adenosine triphosphate (ATP) or lacidipine. Material and Methods: Twenty-four male Wistar rats were randomly assigned to four groups (n = 6 per group): healthy group (HG), atezolizumab (ATZ) group, ATP + atezolizumab (ATAZ) group, and lacidipine + atezolizumab (LCAZ) group. ATP (4 mg/kg, intraperitoneally) or lacidipine (4 mg/kg, orally by gavage) was administered daily for 7 days. Atezolizumab (10 mg/kg, intraperitoneally) was administered twice during the 1-week protocol. On day 8, buccal, gastric, and small-intestinal tissues were evaluated macroscopically and analyzed for oxidative/antioxidant and inflammatory parameters. Histopathological alterations and cleaved caspase-3 immunoreactivity were also assessed. Results: Compared with HG, the ATZ group showed marked oral and GI mucosal alterations accompanied by increased MDA, TNF-α, IL-1β, and IL-6 and decreased tGSH, SOD, and CAT. Co-administration of ATP was associated with attenuation of these changes across a broader range of tissues and outcomes. Lacidipine co-administration was also associated with favorable changes, although these varied according to tissue and parameter. Histopathological damage and cleaved caspase-3 immunoreactivity were increased in the ATZ group and were lower to varying degrees in the co-treatment groups. Conclusions: Under the experimental conditions used, co-administration of ATP or lacidipine with atezolizumab was associated with differences in oxidative, inflammatory, histopathological, and cleaved caspase-3 immunoreactivity compared with atezolizumab alone. ATP-associated changes were observed across a broader range of evaluated outcomes, whereas those associated with lacidipine were more tissue-dependent. Further studies incorporating appropriate formulation/isotype and treatment-only controls are required to establish independent protective effects and clarify their mechanisms and translational relevance.