Cadmium (Cd) is a common environmental pollutant that threatens humans’ and animals’ health. Non-steroidal anti-inflammatory
drugs (NSAIDs) are widely used drugs due to their wide therapeutic action; however, they have significant side effects. Since, under
many circumstances, humans and animals may be co-exposed to Cd andNSAIDs, the current investigationwas assigned to explore the
intertwining relationship between Cd and NSAIDs. Four groups of maleWister rats were used: control group: rats received saline; Cd
group: rats received cadmium (Cd, 2mg/kg) orally; Px group: rats received a NSAID (piroxicam, Px, 7mg/kg, i.p.); and Cd+Px group:
rats received both Cd+Px. All treatments were given once a day for 28 consecutive days. Then, blood samples, stomach, liver, and
kidney tissues were collected. The results indicated that Px provoked gastric ulcer indicated by high ulcer index, while Cd had no effect
on the gastric mucosa. In addition, treatment with Cd or Px alone significantly induced liver and kidney injuries indicated by serum
elevations of AST, ALT, ALP, ALB, total protein, creatinine, and urea along with histopathological alterations. Significant increases in
malondialdehyde and reduction inGSH and CATcontents were reported along with up-regulated expression of Bax and Bcl-2 after Cd
or Px exposure. However, when Cd and Px were given in a combination, Cd obviously potentiated the Px-inflicted cellular injury and
death in the liver and kidney but not in the stomach when compared to their individual exposure. This study concluded that oxidative
stress mechanisms were supposed to be the main modulator in promoting Cd and Px toxicities when given in combination.