Tramadol is an
analgesic used to treat moderate to severe
pain caused by
cancer,
osteoarthritis, and other
musculoskeletal diseases.
Cytochrome P450 system metabolizes
tramadol and induces oxidative stress in different organs. Therefore, the present study aims at investigating the changes in the activities and the
protein expressions of CYPs
isozymes (2E1, 3A4, 2B1/2),
antioxidants status,
free radicals levels after pretreatment of rats with
Curcumin and/or Gallic as single- and/or repeated-doses before administration of
tramadol. In repeated-dose treatments of rats with
tramadol, the activities of
cytochrome P450,
cytochrome b5, and
NADPH-cytochrome-c-reductase, and the
antioxidant enzymes including
glutathione reductase,
glutathione peroxidase,
glutathione S-transferase,
catalase,
superoxide dismutase, and levels of
glutathione were inhibited in the liver and the kidney of rats. Interestingly, such changes caused by
tramadol restored to their normal levels after pretreatment of rats with either
Curcumin and/or
Gallic acid. On the other hand, repeated-dose treatment of rats with
tramadol increased the activities of both
dimethylnitrosamine N-demethylase I (DMN-dI), and aryl
hydrocarbon hydroxylase (AHH) compared to the control group. However, pretreatment of rats with
Curcumin and/or
Gallic acid prior to administration of
tramadol restored the inhibited DMN-dI activity and its
protein expression (
CYP 2E1) to their normal levels. On the other hand,
tramadol inhibited the activity of
ethoxycoumarin O-deethylase (ECOD) and suppressed its
protein marker expression (
CYP2B1/2), whereas
Curcumin,
Gallic acid and/or their mixture restored such changes to their normal levels. In conclusion,
Curcumin and/or
Gallic acid alleviated the adverse effects caused by
tramadol. In addition, patients should be advice to take
Curcumin and/or
Gallic acid prior to
tramadol treatment to alleviate the hepatic and renal toxicities caused by
tramadol.