Prophylactic Effect of Lipoic Acid Against Adriamycin-Induced Peroxidative Damages in Rat Kidney

Malarkodi, Kumaravel Palanichamy; Balachandar, Andithangal Venkatesan; Sivaprasad, R.; Varalakshmi, P.

doi:10.1081/jdi-120021151

Cited by 7 publications

(6 citation statements)

References 38 publications

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“…An additional benefi cial effect of ␣ -lipoic acid on the heart was already reported in rats exposed to adriamycin [28,29] . A similar protective mechanism was observed in erythrocytes [30] and the kidney [31] .…”

Section: Discussionsupporting

confidence: 59%

Decrease in NADPH-Cytochrome P450 Reductase Activity of the Human Heart, Liver and Lungs in the Presence of Alpha-Lipoic Acid

Dudka¹

2006

Ann Nutr Metab

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Background: NADPH-cytochrome P450 reductase (CPR) is the electron donor protein for several oxygenase enzymes located in the endoplasmic reticulum. These oxygenases include P450 family enzymes involved in the metabolism of endogenous and exogenous substances. The enzyme is involved in adriamycin (anticancer drug) and paraquat (herbicide) toxicity. CPR is a flavoprotein containing both flavine-adenine dinucleotide and flavine mononucleotide. A structural study showed the presence of several sulfhydryl (SH) groups in the CPR molecule. Some of them play a key role in catalytic activity. As α-lipoic acid contains a disulfide bond, it may react with the SH group of CPR. The aim of the study was to evaluate the effect of α-lipoic acid on human P450 reductase activity. Methods: The activity of the enzyme was determined by measuring the rate of cytochrome c reduction at 550 nm, in vitro, using heart, liver and lung microsomes. Results: The activity of CPR was decreased in all organs after addition of α-lipoic acid to the reaction mixture at concentrations of 0.01, 0.10 and 1.00 mM. The decreases in CPR activity were concentration-dependent and the sequence of relative inhibition was as follows: heart >lung >liver. However, the statistical significance of CPR activity vs. control was observed in the heart in the presence of 1.00 mM α-lipoic acid and in the lung at 0.10 and 1.00 mM α-lipoic acid. Conclusion: α-Lipoic acid decreased NADPH-CPR activity in the lung and heart. The present results are promising for future studies to obtain the most effective antidote for adriamycin and paraquat toxicity.

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Section: Discussionsupporting

confidence: 59%

Decrease in NADPH-Cytochrome P450 Reductase Activity of the Human Heart, Liver and Lungs in the Presence of Alpha-Lipoic Acid

Dudka¹

2006

Ann Nutr Metab

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“…38 Mitochondrial degeneration and dysfunction has been reported on ADRinduced toxicity. 2,3,6,9 The impaired mitochondrial function may contribute to the pathogenesis of ADR nephrotoxicity, so that we now provided evidence for an additional mechanism of ACE inhibitor to ameliorate ADR nephrotoxicity via the restoration of mitochondrial function and attenuation of ROS in the present study. ADR-treated rats with both ACE and renin inhibitors were observed to have higher levels of MMP, slightly depletion of mitochondrial ATP levels, and less oxidative stress as compared to animals' treatment of ADR alone.…”

Section: Discussionmentioning

confidence: 51%

“…The ADR is accumulated in the kidney, and its concentration in the kidney nuclei and mitochondria is much higher than that observed in the heart. 2,3 Mitochondria may have been suggested to be a primary target of ADR-induced toxicity at the subcellular level. 6,9,38 The ADR also has the tremendous ability to inhibit oxidative phosphorylation, which may account for the impairment of energy metabolism of the cell inhibition of electron transport complexes, and disruption of calcium homeostasis.…”

Section: Discussionmentioning

confidence: 99%

The restoration of kidney mitochondria function by inhibition of angiotensin-II production in rats with acute adriamycin-induced nephrotoxicity

et al. 2014

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Adriamycin (ADR) is commonly used for many solid tumor treatments. Its clinical utility is, however, largely limited by the adverse reactions, are known to be nephrotoxic. The mechanism by which it induces kidney damage is still not completely understood, but its nephrotoxicity might relate to increase reactive oxidant status (ROS), mitochondrial dysfunction. Until now, neurohormonal activation of it is unclear. ADR might activate the renin angiotensin system. Angiotensin-II also induced ROS and mitochondrial dysfunction. The aim of this study was to investigate whether angiotensin-II production inhibition has the protective effect on attenuation of mitochondrial function in rats with acute ADR-nephrotoxicity or not. Rats were divided into five groups as a control, ADR, co-treated ADR with captopril (CAP), co-treated ADR with Aliskren, co-treated ADR with both CAP and Aliskren groups. Creatinine kinase (CK) levels were measured at the end of treatment period. The kidneys were homogenized and biochemical measurements were made in mitochondria, cytosol. Mitochondria membrane potential (MMP) and ATP levels were determined. ADR increased CK levels and oxidative stress in mitochondria too (p50.05). ADR significantly decreased MMP and ATP level in kidney mitochondria (p50.05). Co-administration with ADR and Aliskren and CAP improved the dissipation of MMP (p50.05). The decrease in ATP level was restored by treatment with inhibitors of ACE and renin. We concluded that inhibitors of angiotensin-II are effective against acute ADR induced nephrotoxicity via the restoration of MMP and ATP production and prevention of mitochondrial damage in vivo. KeywordsAdriamycin-induced nephrotoxicity, Aliskren, captopril, mitochondrial ATP, mitochondrial membrane potential, oxidative stress index History

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“…Cancer treatment is usually accompanied by diverse side effects to different body organs. The use of adriamycin, a potent anticancer agent with efficacy in a broad range of malignancies, is limited by severe cytotoxic side effects, the most important being cardiotoxicity [1,39] and nephrotoxicity [4,40]. Adriamycin‐induced nephrotoxicity in rats revealed a severe nephropathy with substantial hyperlipidaemia, hypoproteinaemia and proteinuria (Table 1 and Figure 1).…”

Section: Discussionmentioning

confidence: 99%

Ginkgo biloba leaf extract (EGb 761) diminishes adriamycin‐induced hyperlipidaemic nephrotoxicity in rats: association with nitric oxide production

Abd-Ellah

Mariee

2007

Biotech and App Biochem

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The aim of this experimental study was to investigate the effect of a standardized preparation of Ginkgo biloba extract (EGb 761) on the hyperlipidaemic nephrotoxicity and oxidative stress induced by a single intravenous injection (5 mg/kg) of adriamycin. EGb 761 was received daily thereafter by a gavage at the dose of 100 mg/kg for 35 consecutive days. EGb 761 administration significantly attenuated adriamycin-induced renal dysfunction, as assessed by measuring serum lipid profile, serum total protein, serum urea and Ccr (creatinine clearance). Furthermore, urinary excretions of protein and NAG (N-acetyl-beta-D-glucosaminidase; a marker of renal tubular injury) were significantly inhibited following EGb 761 administration. EGb 761 supplementation significantly prevented the generation of TBARS (thiobarbituric acid-reacting substances) with a marked improvement in terms of GSH content and activity of antioxidant enzymes in the kidney homogenate. Moreover, EGb 761 treatment significantly reduced both renal-tissue and urine total NO (nitric oxide) levels. The results suggest that the protective potential of EGb 761 in the prevention of adriamycin-induced hyperlipidaemic nephrotoxicity in rats was associated with the decrease in the oxidative stress and the total NO levels of renal tissues. Likewise, the present study demonstrates the ability of EGb 761 to reduce the hyperlipidaemia and proteinuria associated with this nephropathy, which might be beneficial to enhance the therapeutic index of adriamycin.

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Prophylactic Effect of Lipoic Acid Against Adriamycin-Induced Peroxidative Damages in Rat Kidney

Abstract: This study has highlighted the beneficial effects of LA pretreatment in reversing the damages caused by ADR, by bringing about an improvement in the reductive status of the cell.

Cited by 7 publications

References 38 publications

Decrease in NADPH-Cytochrome P450 Reductase Activity of the Human Heart, Liver and Lungs in the Presence of Alpha-Lipoic Acid

Decrease in NADPH-Cytochrome P450 Reductase Activity of the Human Heart, Liver and Lungs in the Presence of Alpha-Lipoic Acid

The restoration of kidney mitochondria function by inhibition of angiotensin-II production in rats with acute adriamycin-induced nephrotoxicity

Ginkgo biloba leaf extract (EGb 761) diminishes adriamycin‐induced hyperlipidaemic nephrotoxicity in rats: association with nitric oxide production

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