Curcumin prevents free radical-mediated cataractogenesis through modulations in lens calcium.
The generation of free radicals has been implicated in the causation of cataract, and compounds that can scavenge free radicals ameliorate the disease process. This study investigated the possible free radical scavenging potential of curcumin at a dose of 75 mg/kg body wt on selenium-induced cataract in rat pups. Intraperitoneal injection of sodium selenite (15 micromol/kg body wt) into 8- to 10-day-old rat pups led to severe oxidative stress in the eye lens as evidenced by increased nitric oxide, superoxide anion, and hydroxyl radical generation and inducible nitric oxide synthase expression that probably led to cataract formation. Selenium exposure also caused an increase in total calcium in the eye lens and significantly inhibited the activity of Ca(2+) ATPase but not Na(+)/K(+) ATPase or Mg(2+) ATPase. On the other hand, pretreatment with curcumin, but not simultaneous or posttreatment, led to a decrease in oxidative stress and also rescued the selenium-mediated increase in lens Ca(2+) and inhibition of Ca(2+) ATPase activity in the eye lens. The results of this study demonstrate that an increase in free radical generation triggered by selenium could cause inactivation of lens Ca(2+) ATPase leading to Ca(2+) accumulation. This enhanced Ca(2+) can cause activation of calpain-mediated proteolysis in the lens, resulting in lens opacification. Curcumin in this study was able to prevent selenium-induced oxidative stress leading to activation of Ca(2+) ATPase and inhibition of lens opacification. Thus, curcumin has the potential to function as an anticataractogenic agent, possibly by preventing free radical-mediated accumulation of Ca(2+) in the eye lens.
Manikandan
Ramar
R
Department of Zoology, Unit of Pathobiology, University of Madras, Guindy Campus, Chennai 600 025, India. manikandanramar@yahoo.co.in
Thiagarajan
Raman
R
Beulaja
Sivagnanam
S
Sudhandiran
Ganapasam
G
Arumugam
Munuswamy
M
D000818:Animals; D001835:Body Weight; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000737:chemistry; D002386:Cataract / Q000188:drug therapy* / Q000517:prevention & control*; D003474:Curcumin / Q000494:pharmacology*; D005609:Free Radicals; D017665:Hydroxyl Radical / Q000737:chemistry; D007908:Lens, Crystalline / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012643:Selenium / Q000737:chemistry / Q000494:pharmacology
D005609:Free Radicals; D017665:Hydroxyl Radical; D000252:Calcium-Transporting ATPases; D012643:Selenium; D003474:Curcumin; D010100:Oxygen; D002118:Calcium