Dose‐dependent actions of curcumin in experimentally induced myocardial necrosis: a biochemical, histopathological, and electron microscopic evidence

Abstract

Curcumin, an active component of turmeric, is a well-known antioxidant due to its reactive oxygen species (ROS) scavenging property. However, some in vitro studies have suggested that curcumin induces generation of ROS at higher doses and thus exerts pro-oxidant effect. We demonstrate, for the first time, the dose-dependent effects of curcumin in isoprenaline-induced model of myocardial necrosis in rats. The animals were assigned to control, isoprenaline and three curcumin treatment groups. Curcumin (100, 200, and 400 mg/kg) and vehicle (dimethyl sulfoxide) were administrated orally for 15 days and isoprenaline (85 mg/kg, s.c.) was given to curcumin treated and isoprenaline group on 13th and 14th day, respectively. Thereafter, on 15th day, the animals were sacrificed for biochemical analysis along with histopathological and ultrastructural examination. There was an increase in glutathione, superoxide dismutase (SOD), creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) levels, decrease in thiobarbituric acid reactive substances (TBARS), and preservation of myocardial architecture in the curcumin (100 and 200 mg/kg) treated groups. However, at 400 mg/kg dose there was ineffectual protection against isoprenaline-induced myocardial damage. Instead, there was significant lipid peroxidation as evident by increased levels of TBARS (93.87 +/- 9.93, p < 0.0001) and decrease in CK-MB (206.32 +/- 13.54, p < 0.0001) and LDH (134.26 +/- 9.13, p < 0.01) as compared to the two lower doses. Hence, it can be concluded that curcumin augments endogenous antioxidant system at lower doses but mediates ROS induction at higher concentration leading to myocardial damage.

Studies on the ameliorative effect of curcumin on carbofuran induced perturbations in the activity of lactate dehydrogenase in wistar rats

“…In the present study curcumin was observed to alleviate the adverse effects of carbofuran on rat brain. Similar ameliorative effects of curcumin have been described by other workers (Tanwar et al, 2010). Though there are reports indicating the antioxidative and pro-oxidative properties of curcumin at lower and higher doses, respectively, the exact mechanism of interaction of curcumin with LDH is not known (Tanwar et al, 2010).…”

Phenolic Compounds Exerting Lipid-Regulatory, Anti-Inflammatory and Epigenetic Effects as Complementary Treatments in Cardiovascular Diseases

“…The antioxidant action of curcumin resides in the inhibition of ROS production by repressing the catalytic subunits p67phox, p47phox and p22phox of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase [52,53]. In parallel, curcumin reduces ROS by upregulating the expression of endogenous antioxidant enzymes, such as SOD, catalase, GSH-Px and HO-1 [54,55]. Another interesting mechanism by which curcumin exerts antioxidant effects is the preservation of the mitochondrial redox potential [13] that has been evidenced in vivo in rat hearts subjected to ischemia-reperfusion.…”

A Comprehensive Behavioural Assessment of Curcumin’s Effect on Inflammatory and Non-Inflammatory Pain in Mice

“…It is possible that the smaller dose was too small to generate a significant effect, especially since the low bioavailability of oral curcumin is well-known [18]. The larger dose (300 mg/kg bw) was also inefficient, possibly due to the pro-inflammatory effects of large doses of curcumin [19]; the 300 mg/kg bw dose administered in our study is approximately 1.7 grams when converted to human equivalent dose [20,21], which is significantly larger than the average doses used in clinical studies. The dose of 120 mg/kg bw induced a persistent antinociceptive effect in the Tail Flick test over a 3 hour period with a maximum effect at one hour.…”