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Abstract

The main purpose of this study was to investigate the effect of free radicals and experimental diabetes on cytosolic creatine kinase activity in rat heart, muscle and brain. Hydrogen peroxide decreased creatine kinase activity in a dose dependent manner which was reversed by catalase. Xanthine/xanthine oxidase, which produces superoxide anion, lowered the creatine kinase activity in the same manner whose effect was protected by superoxide dismutase. N-acetylcysteine and dithiothreitol also significantly ameliorated the effect of Xanthine/xanthine oxidase and hydrogen peroxide. Experimental diabetes of twenty-one days (induced by alloxan), also caused a similar decrease in the activity of creatine kinase. This led us to the conclusion that the decrease in creatine kinase activity during diabetes could be due to the production of reactive oxygen species. The free radical effect could be on the sulfhydryl groups of the enzyme at the active sites, since addition of sulfhydryl groups like N-acetylcysteine and dithiothreitol showed a significant reversal effect.

Role of xanthine oxidoreductase in cardiac nitroso-redox imbalance

“…A number of ex vivo studies supports a role for XOR in the impairment of myocardial energetics in HF (36, 57). XOR reduces CK activity in rat hearts in vitro through the production of O 2 − (36).…”

“…O 2 − can also generate peroxynitrite by interacting with NO (5). O 2 − is converted by superoxide dismutase (SOD) to H 2 O 2 , which is less potent but can also exert cardiotoxic effects (5, 36). H 2 O 2 can also convert to OH − through the Fenton reaction (H 2 O 2 + Fe 2+ → OH − + OH − + Fe 3+ ) and this conversion was shown to occur in myocardial tissue obtained from animal models of heart failure (22, 36).…”

“…XOR reduces CK activity in rat hearts in vitro through the production of O 2 − (36). H 2 O 2 also suppressed CK activity in the same report (36).…”

“…XOR reduces CK activity in rat hearts in vitro through the production of O 2 − (36). H 2 O 2 also suppressed CK activity in the same report (36). Moreover, OH − reduced the ATP content of cardiomyocytes in vitro (57).…”

POSSIBLE MECHANISM OF <i>PLUMBAGO ZEYLANICA</i> IN PREVENTION OF HEPATIC DAMMAGE IN WISTAR RAT

“…Increased Nitric Oxide (NO) expression in hepatocytes, hepatic macrophages and kupffer cells after activation with various toxic stimuli (Guler et al, 2004), initiates the cascades of free radical mediated necrotic and apoptotic reactions (Jaeschke et al, 2002). The toxic effects of oxidative stimuli result increased cell damage characterized by decreased GSH and SOD levels (Genet et al, 2000). Glutathione and superoxide dismutase (Husain and Somani, 1997) play the important role in detoxification of toxic reactive metabolites (Pigeolet et al, 1990).…”