Calcium Channel Blockade in Experimental Aminoglycoside Nephrotoxicity

Watson, Alan J.; Gimenez, Luis F.; Klassen, David K.; Stout, Robert L.; Whelton, Andrew

doi:10.1002/j.1552-4604.1987.tb03076.x

Cited by 20 publications

(3 citation statements)

References 7 publications

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“…[ 13 ] None of the above agents has truly established itself in clinical practice. Previous studies using calcium channel blockers such as verapamil have shown contradictory results in gentamicin-induced nephrotoxicity with some showing a beneficial effect[ 14 ] while others have shown a nephrotoxicity enhancing potential. [ 15 16 ] A recent study has shown a beneficial effect of oral calcium (Ca +2 ) administration in gentamicin-induced nephrotoxicity in rats.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the species-sensitive effects of different dosages of calcium and verapamil on gentamicin-induced nephrotoxicity in rats and rabbits

Patil¹,

Arora²,

Desai³

et al. 2014

Toxicol Int

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Aim:To compare the effects of different dosages of calcium and verapamil on gentamicin-induced nephrotoxicity in rats and rabbits.Materials and Methods:Rabbits and rats of either sex in weight range of 1.5–2.5 kg and 175–225 g, respectively were used in study. Gentamicin 80 mg/kg i.m., calcium carbonate 0.5 g/kg/day oral, calcium carbonate 1.0 g/kg/day oral, and verapamil 7 mg/kg/day i.m. were administered for 6 days in either species containing 7 groups. Blood urea nitrogen (BUN), serum creatinine and, urine protein levels were assessed on day 0 and day 7 for kidney function. The animals were sacrificed on day 7 for histopathplogical examination and kidney superoxide dismutase levels (SOD) were measured. Statistical analysis was done using student's unpaired t-test, analysis of variance (ANOVA) and Wilcoxon Rank Sum test. P-value less than 0.05 was considered significant.Results:The results showed that calcium was able to reverse significantly increased BUN, serum creatinine, urine protein, and reduced kidney SOD levels in gentamicin-treated nephrotoxic rats or rabbits in a dose-dependent manner while verapamil had no protective or nephrotoxic effect.Conclusion:Calcium 0.5 g/kg/day and 1.0 g/kg/day were able to reverse tubular necrosis and mesangial proliferation in gentamicin-treated nephrotoxic animals. There was no species-sensitive variation in reversal of nephrotoxicity by calcium in rats and rabbits.

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Section: Introductionmentioning

confidence: 99%

Comparison of the species-sensitive effects of different dosages of calcium and verapamil on gentamicin-induced nephrotoxicity in rats and rabbits

Patil¹,

Arora²,

Desai³

et al. 2014

Toxicol Int

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“…For example, large renal blood flow and therefore a higher relative exposure to toxic effects, including higher oxygen uptake, sensitivity of renal tissues to hypoxia, and degree of permeability of proximal tubules. As for the presence of verapamil, it is a protective association from toxicity, preventing the flow of calcium to the damaged cells and reducing the renal blood flow, thus mitigating the development of acute renal failure (6). As for garlic, Allium sativum belongs to the Aillaceae family, and it is considered the second most important green crop, second in sequence after onions, and it is likely that its area of origin is an Asian region It is a green vegetable crop with abundant nutritional and medicinal benefits, as its cloves contain 31% carbohydrates and 2.6% proteins based on wet weight.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the therapeutic role of garlic extract and verapamil against gentamicin-induced nephrotoxicity in rats

2022

pnr

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Background: The aminoglycoside group, especially gentamicin, is the critical antibiotic in severe Gram-negative bacterial infections through its significant risk of nephrotoxicity. There are many protective factors for the kidneys, including blocking the flow of calcium to the damaged cells of the kidneys and reducing renal blood flow through the drug verapamil, In the same regard, garlic has been proven to be an antioxidant, a natural plant remedy for kidney protection.Aim of the study: Knowledge of enzymatic changes in the kidney due to gentamicin treatment and the role of garlic alcohol extract and verapamil in improving these changes.Methods and materials: 40 rats (3 to 6 months old) were brought up at normal temperature and divided into four equal groups, each group included 10 rats, including the negative control group, which were given orally 0.9% physiological salt solution, and the second group, the positive control (treated with G) 80 mg/kg by intraperitoneal injection, and the third group was given (G) 80 mg/kg intraperitoneally with (V) 3 mg/kg orally, And the fourth group had been injected with (G) 80 mg/kg intraperitoneally with (GAE) 20 mg/kg orally. The study included the evaluation of some biochemical blood parameters, including: levels of creatinine, urea, total protein, sodium, potassium, malondialdehyde (MDA), glutathione (GSH), and catalase (CAT). Above these criteria were the study of the median lethal dose (LD50).Results: The statistical analysis of the results showed: -The results of the current study, through the results of the statistical analysis, showed a significant increase (P<0.05) in the effectiveness of the levels of urea, creatinine, sodium, Dimalone Dehyde (MDA) when comparing the positive control group treated with (G) at a concentration of 80 mg/ In contrast, the levels of total protein, potassium, glutathione (GSH), catalase (CAT) significantly decreased (P<0.05) in the positive control group when compared with the other experimental groups.Conclusion: Garlic alcoholic extract and verapamil are highly effective in protecting blood biochemical parameters from gentamicin-induced nephrotoxicity.

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“…In models of aminoglycoside toxicity, contradictory results have been published. Calcium channel blockers have been reported to be of no use (9,18,43), to exhibit a deleterious effect (17), or again, to be efficient (25,35) in * Corresponding author. preventing renal failure.…”

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confidence: 99%

Effects of diltiazem on netilmicin-induced nephrotoxicity in rabbits

Lortholary

Blanchet

Nochy

et al. 1993

Antimicrob Agents Chemother

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Aminoglycoside nephrotoxicity remains a common clinical problem and is the major cause of acute toxic renal failure in hospitalized patients. In recent studies, calcium channel blockers gave controversial results in the prevention of acute ischemic or toxic renal failure. The aims of the study were (i) to describe a rabbit model of mild renal failure (50%o reduction in glomerular filtration rate with a mean value of 1.78 0.46 ml/kg/min) induced by netilmicin given intramuscularly at 20 mg/kg of body weight every 8 h for 5 days, (ii) to investigate the protective effect of diltiazem given at a therapeutic dose (1 mg/kg given intramuscularly every 8 h for 5 days), and (iii) to investigate the mechanisms of this protection through evaluation of function tests, optic histology, and glomerular morphometry. Animals treated with netilmicin and diltiazem exhibited an unchanged glomerular filtration rate compared with controls (3.39 + 0.58 versus 3.68 -0.78 ml/kg/min, respectively). This protective effect was not associated with any change in systemic or renal hemodynamics (i.e., no change in renal plasma flow) or changes in the pharmacokinetics of netilmicin, as assessed by fractional excretion and cortical uptake. Netilmicin-induced tubular toxicity was unchanged by diltiazem. Our results suggest that (i) netilmicin exhibits a toxic effect at both the glomerular and the tubular levels, (ii) diltiazem, a calcium channel blocker, when given at low therapeutic doses, is able to prevent the aminoglycoside-induced renal failure through a potential glomerular mechanism. The precise mechanisms of the protection remain to be elucidated. These results deserve clinical evaluation in high-risk patients. (5,21,24). In models of aminoglycoside toxicity, contradictory results have been published. Calcium channel blockers have been reported to be of no use (9,18,43), to exhibit a deleterious effect (17), or again, to be efficient (25, 35) in * Corresponding author. preventing renal failure. In those studies in rats, aminoglycoside and calcium channel blocker doses were high and gentamicin, one of the most nephrotoxic aminoglycosides, was frequently used.We have observed, in human volunteers, that diltiazem (60 mg given three times a day for 7 days) could prevent the increase in urinary N-acetylglucosaminidase (NAG) levels and the loss of dilution ability induced by netilmicin (4.5 mg/kg of body weight given once daily for 7 days) (30). However, in studies performed in humans, it is difficult to investigate the precise mechanisms of such protective effects (37).The aims of the present study were (i) to describe a rabbit model of moderate renal failure induced by netilmicin at the lowest dose that induced a toxic effect (a regimen of three injections per day was chosen to increase the toxic potential over a short period of time [5 days]), (ii) to investigate the protective effect of diltiazem given at therapeutic doses, and (iii) to elucidate at which level protection could occur.Both drugs were chosen because they have previously bee...

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Calcium Channel Blockade in Experimental Aminoglycoside Nephrotoxicity

Cited by 20 publications

References 7 publications

Comparison of the species-sensitive effects of different dosages of calcium and verapamil on gentamicin-induced nephrotoxicity in rats and rabbits

Comparison of the species-sensitive effects of different dosages of calcium and verapamil on gentamicin-induced nephrotoxicity in rats and rabbits

Comparison of the therapeutic role of garlic extract and verapamil against gentamicin-induced nephrotoxicity in rats

Effects of diltiazem on netilmicin-induced nephrotoxicity in rabbits

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