Antibiotics: Adverse effects and treatment
http://www.ummafrapp.de/skandal/felix/NAC/Beilage3.pdf
J Antimicrob Chemother. 2009 Oct;64(4):850-2. Epub 2009 Aug 4.
Influence of concomitant prednisolone on
trimethoprim-associated hyperkalaemia.
Mohan S, Jaitly M, Pogue VA, Cheng JT.
Source
Columbia University College of Physicians and Surgeons, Department of Medicine, Division
of Nephrology, Harlem Hospital Center, 506 Lenox Avenue, New York, NY 10037, USA.
sm2206@columbia.edu
Abstract
OBJECTIVES:
Trimethoprim-sulfamethoxazole may cause hyperkalaemia by the amiloride-like effect of
trimethoprim on sodium channels in the distal nephron. Hyperkalaemia usually occurs after 710 days and has been reported in 20%-50% of patients receiving trimethoprimsulfamethoxazole. Patients with Pneumocystis jiroveci pneumonia and severe hypoxaemia
benefit from the use of prednisolone as an adjuvant to trimethoprim-sulfamethoxazole. The
addition of prednisolone may lower the incidence of trimethoprim-related hyperkalaemia due,
in part, to its mineralocorticoid activity. We studied the effect of concomitant prednisolone on
trimethoprim-related hyperkalaemia.
PATIENTS:
Thirty patients qualified for inclusion and were reviewed. Patients were divided into two
groups: one group received trimethoprim-sulfamethoxazole plus prednisolone (18 patients);
and the other group received trimethoprim-sulfamethoxazole alone (12 patients).
RESULTS:
The two groups were comparable at baseline, except for the severity of the P. jiroveci
pneumonia. Hyperkalaemia developed in seven patients: all in the prednisolone and
trimethoprim-sulfamethoxazole group. The greater incidence of hyperkalaemia in this group
is surprising and was counter to our expectation.
CONCLUSIONS:
Although it is possible that there is an unexplained interaction between trimethoprim and
prednisolone, we postulate that our observation is a result of the catabolic effect of
prednisolone. The patients treated with trimethoprim-sulfamethoxazole plus prednisolone
appear to be more likely to develop hyperkalaemia than patients treated with trimethoprimsulfamethoxazole alone.
Supplemental Content
Respirology. 2008 Mar;13(2):294-8.
Links
Effect of vitamin E and selenium supplementation on
oxidative stress status in pulmonary tuberculosis
patients.
Seyedrezazadeh E, Ostadrahimi A, Mahboob S, Assadi Y, Ghaemmagami J,
Pourmogaddam M.
Faculty of Health and Nutrition, Tabriz University of Medical Sciences, Tabriz
Azarbayegan Shargi, Iran. esrz80@yahoo.com
BACKGROUND AND OBJECTIVE: Increased production of reactive oxygen
species secondary to phagocyte respiratory burst occurs in pulmonary tuberculosis
(TB). The present study evaluated the efficacy of vitamin E-selenium supplementation
on oxidative stress in newly diagnosed patients treated for pulmonary TB.
METHODS: A double-blind, placebo-controlled trial including patients with newly
diagnosed TB was conducted. The intervention group (n = 17) received vitamin E and
selenium (vitamin E: 140 mg alpha-tocopherol and selenium: 200 microg) and the
control group (n = 18) received placebo. Both groups received standard anti-TB
treatment. Assessment of micronutrient levels, oxidative markers and total antioxidant
capacity were carried out at baseline and 2 months after the intervention. RESULTS:
Malondialdehyde levels were significantly reduced in the intervention group (P =
0.01), while there was minimal reduction in the control group. The mean plasma level
of total antioxidants was increased significantly (P = 0.001) in both the intervention
and the control groups. CONCLUSION: A 2-month intervention with vitamin E and
selenium supplementation reduces oxidative stress and enhances total antioxidant
status in patients with pulmonary TB treated with standard chemotherapy.
PMID: 18339032 [PubMed - indexed for MEDLINE]
Life Sci. 2008 Aug 1;83(5-6):155-63. Epub 2008 Jun 18.
Links
Dapsone induces oxidative stress and impairs
antioxidant defenses in rat liver.
Veggi LM, Pretto L, Ochoa EJ, Catania VA, Luquita MG, Taborda DR, Sánchez Pozzi
EJ, Ikushiro S, Coleman MD, Roma MG, Mottino AD.
Facultad de Ciencias Bioquímicas y Farmacéuticas, Instituto de Fisiología
Experimental, U.N.R.-CONICET, Rosario, Argentina.
Dapsone (DDS) is currently used in the treatment of leprosy, malaria and in infections
with Pneumocystis jirovecii and Toxoplasma gondii in AIDS patients. Adverse effects
of DDS involve methemoglobinemia and hemolysis and, to a lower extent, liver
damage, though the mechanism is poorly characterized. We evaluated the effect of
DDS administration to male and female rats (30 mg/kg body wt, twice a day, for 4
days) on liver oxidative stress through assessment of biliary output and liver content of
reduced (GSH) and oxidized (GSSG) glutathione, lipid peroxidation, and
expression/activities of the main antioxidant enzymes glutathione peroxidase,
superoxide dismutase, catalase and glutathione S-transferase. The influence of DDS
treatment on expression/activity of the main DDS phase-II-metabolizing system,
UDP-glucuronosyltransferase (UGT), was additionally evaluated. The involvement of
dapsone hydroxylamine (DDS-NHOH) generation in these processes was estimated by
comparing the data in male and female rats since N-hydroxylation of DDS mainly
occurs in males. Our studies revealed an increase in the GSSG/GSH biliary output
ratio, a sensitive indicator of oxidative stress, and in lipid peroxidation, in male but not
in female rats treated with DDS. The activity of all antioxidant enzymes was
significantly impaired by DDS treatment also in male rats, whereas UGT activity was
not affected in any sex. Taken together, the evidence indicates that DDS induces
oxidative stress in rat liver and that N-hydroxylation of DDS was the likely mediator.
Impairment in the activity of enzymatic antioxidant systems, also associated with
DDS-NHOH formation, constituted a key aggravating factor.
Clin Pharmacol Ther. 2004 Oct;76(4):313-22.
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The effect of clarithromycin, fluconazole, and
rifabutin on sulfamethoxazole hydroxylamine
formation in individuals with human
immunodeficiency virus infection (AACTG 283).
Winter HR, Trapnell CB, Slattery JT, Jacobson M, Greenspan DL, Hooton TM,
Unadkat JD.
University of Washington, Seattle 98195, USA.
BACKGROUND: Sulfamethoxazole hydroxylamine formation, in combination with
long-term oxidative stress, is thought to be the cause of high rates of adverse drug
reactions to sulfamethoxazole in human immunodeficiency virus (HIV)-infected
subjects. Therefore the goal of this study was to determine the effect of fluconazole,
clarithromycin, and rifabutin on sulfamethoxazole hydroxylamine formation in
individuals with HIV-1 infection. METHODS: HIV-1-infected subjects (CD4 + count
>/=200 cells/mm 3 ) were enrolled in a 2-part (A and B), open-label drug interaction
study (Adult AIDS Clinical Trial Group [AACTG] 283). In part A (n = 9), subjects
received cotrimoxazole (1 tablet of 800 mg sulfamethoxazole/160 mg trimethoprim
daily) alone for 2 weeks and then, in a randomly assigned order, cotrimoxazole plus
either fluconazole (200 mg daily), rifabutin (300 mg daily), or fluconazole plus
rifabutin, each for a 2-week period. Part B (n = 12) was identical to part A except that
clarithromycin (500 mg twice daily) was substituted for rifabutin. RESULTS: In part
A, fluconazole decreased the area under the plasma concentration-time curve (AUC),
percent of dose excreted in 24-hour urine, and formation clearance (CL f ) of the
hydroxylamine by 37%, 53%, and 61%, respectively (paired t test, P < .05). Rifabutin
increased the AUC, percent excreted, and CL f of the hydroxylamine by 55%, 45%,
and 53%, respectively ( P < .05). Fluconazole plus rifabutin decreased the AUC,
percent excreted, and CL f of the hydroxylamine by 21%, 37%, and 46%, respectively
( P < .05). In part B the fluconazole data were similar to those of part A. Overall,
clarithromycin had no effect on hydroxylamine production. CONCLUSIONS: If the
exposure (AUC) to sulfamethoxazole hydroxylamine is predictive of
sulfamethoxazole toxicity, then rifabutin will increase and clarithromycin plus
fluconazole or rifabutin plus fluconazole will decrease the rates of adverse reactions to
sulfamethoxazole in HIV-infected subjects.
:
Iran J Kidney Dis. 2012 Jan;6(1):25-32.
Inhibitory effect of olive leaf extract on
gentamicin-induced nephrotoxicity in
rats.
Tavafi M, Ahmadvand H, Toolabi P.
Source
Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khoram
Abad, Iran. mtavafi@yahoo.com
Abstract
INTRODUCTION:
Gentamicin sulphate nephrotoxicity seems to be attributed to the generation of reactive
oxygen species. Olive leaf extract (OLE) has been demonstrated to have antioxidant and antiinflammatory effects. The aim of this study was to evaluate the inhibitory effect of OLE on
gentamicin-induced nephrotoxicity in rats.
MATERIALS AND METHODS:
Thirty-five Sprague-dawley rats were divided into 5 groups to receive saline; gentamicin, 100
mg/kg/d; and gentamicin plus OLE in 3 different doses (25 mg/kg/d, 50 mg/kg/d, and 100
mg/kg/d, once daily for 12 days. Serum and renal malondialdehyde were assessed, and tubular
necrosis was studied semiquantitatively. Glomerular volume and volume density of the
proximal convoluted tubules were estimated stereologically from paraffin sections. Serum
creatinine and renal antioxidant enzymes activity were measured.
RESULTS:
Gentamicin significantly increased serum creatinine, malondialdehyde, and tubular necrosis,
and decreased creatinine clearance, volume density of the proximal convoluted tubules, renal
glutathione, glutathione peroxidase, catalase, and superoxide dismutase compared with the
control group. Cotreatment of gentamicin and OLE significantly decreased serum creatinine,
malondialdehyde, tubular necrosis, and renal malondialdehyde, and increased renal
glutathione, catalase, superoxide dismutase, volume density of proximal convoluted tubules,
and creatinine clearance in comparison with gentamicin-only treated group. Serum
malondialdehyde, serum creatinine, tubular necrosis, and volume density of proximal
convoluted tubules were maintained at the same level as that of the control group by
cotreatment of gentamicin and OLE.
CONCLUSIONS:
Olive leaf extract ameliorates gentamicin nephrotoxicity via antioxidant activity, increase of
renal glutathione content, and increase of renal antioxidant enzymes activity, except for
glutathione peroxidase.
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Supplemental Content
BMC Complement Altern Med. 2011 Nov 15;11:113.
Prevention of hepatorenal toxicity with
Sonchus asper in gentamicin treated rats.
Khan MR, Badar I, Siddiquah A.
Source
Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University
Islamabad 44000, Pakistan. mrkhanqau@yahoo.com
Abstract
BACKGROUND:
Sonchus asper possesses antioxidant capacity and is used in liver and kidney disorders. We
have investigated the preventive effect of methanolic extract of Sonchus asper (SAME) on the
gentamicin induced alterations in biochemical and morphological parameters in liver and
kidneys of Sprague-Dawley male rat.
METHODS:
Acute oral toxicity studies were performed for selecting the therapeutic dose of SAME. 30
Sprague-Dawley male rats were equally divided into five groups with 06 animals in each.
Group I received saline (0.5 ml/kg bw; 0.9% NaCl) while Group II administered with
gentamicin 0.5 ml (100 mg/kg bw; i.p.) for ten days. Animals of Group III and Group IV
received gentamicin and SAME 0.5 ml at a dose of 100 mg/kg bw and 200 mg/kg bw,
respectively while Group V received only SAME at a dose of 200 mg/kg bw. Biochemical
parameters including aspartate transaminase (AST), alanine transaminase (ALT), alkaline
phosphatase (ALP), lactate dehydrogenase (LDH), γ-glutamyltransferase (γ-GT), total
cholesterol, triglycerides, total protein, albumin, creatinine, blood urea nitrogen (BUN), total
bilirubin and direct bilirubin were determined in serum collected from various groups.
Urinary out puts were measured in each group and also assessed for the level of protein and
glucose. Lipid peroxides (TBARS), glutathione (GSH), DNA injuries and activities of
antioxidant enzymes; catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD)
were determined in liver and renal samples. Histopathological studies of liver and kidneys
were also carried out.
RESULTS:
On the basis of acute oral toxicity studies, 2000 mg/kg bw did not induce any toxicity in rats,
1/10th of the dose was selected for preventive treatment. Gentamicin increased the level of
serum biomarkers; AST, ALT, ALP, LDH, γ-GT, total cholesterol, triglycerides, total protein,
albumin, creatinine, BUN, total and direct bilirubin; as were the urinary level of protein,
glucose, and urinary output. Lipid peroxidation (TBARS) and DNA injuries increased while
GSH contents and activities of antioxidant enzymes; CAT, POD, SOD decreased with
gentamicin in liver and kidney samples. SAME administration, dose dependently, prevented
the alteration in biochemical parameters and were supported by low level of tubular and
glomerular injuries induced with gentamicin.
CONCLUSION:
These results suggested the preventive role of SAME for gentamicin induced toxicity that
could be attributed by phytochemicals having antioxidant and free radical scavenging
properties.
Supplemental Content
Int J Cell Biol. 2011;2011:390238. Epub 2011 Jun 16.
Doxorubicin induced nephrotoxicity:
protective effect of nicotinamide.
Ayla S, Seckin I, Tanriverdi G, Cengiz M, Eser M, Soner BC, Oktem G.
Source
Suleymaniye Woman Health Hospital, 34122 Istanbul, Turkey.
Abstract
Introduction. Nephrotoxicity is one of the important side effects of anthracycline antibiotics.
The aim of this study was to investigate the effects of nicotinamide (NAD), an antioxidant
agent, against nephrotoxicity induced by doxorubicin (DXR). Methods. The rats were divided
into control, NAD alone, doxorubicin (20 mg/kg, i.p.) and DXR plus NAD (200 mg/kg, i.p.)
groups. At the end of the 10th day, kidney tissues were removed for light microscopy and
analysis. The level of tissues' catalase (CAT), glutathione (GSH), glutathione peroxidase
(GPx), inducible nitric oxide (iNOS) and endothelial nitric oxide (eNOS) activities were
determined. Results. The activities of CAT, GPx, and GSH were decreased, and Po was
increased in renal tissue of doxorubicin group compared with other groups. The tissue of the
doxorubicin group showed some histopathological changes such as glomerular vacuolization
and degeneration, adhesion to Bowman's capsule and thickening and untidiness of tubular and
glomerular capillary basement membranes. Histopathological examination showed that NAD
prevented partly DXR-induced tubular and glomerular damage. Conclusions. Pretreatment
with NAD protected renal tissues against DXR-induced nephrotoxicity. Preventive effects of
NAD on these renal lesions may be via its antioxidant and anti-inflammatory action.
Supplemental Content
Oxid Med Cell Longev. 2010 Nov-Dec;3(6):428-33. Epub 2010 Nov 1.
Doxorubicin toxicity can be ameliorated
during antioxidant L-carnitine
supplementation.
Alshabanah OA, Hafez MM, Al-Harbi MM, Hassan ZK, Al Rejaie SS, Asiri YA, SayedAhmed MM.
Source
Department of Pharmacology; College of pharmacy, King Saud University, Riyadh Kingdom
of Saudi Arabia. alshabanah@ksu.edu.sa
Abstract
Doxorubicin is an antibiotic broadly used in treatment of different types of solid tumors. The
present study investigates whether L-carnitine, antioxidant agent, can reduce the hepatic
damage induced by doxorubicin. Male Wistar albino rats were divided into six groups: group
1 were intraperitoneal injected with normal saline for 10 consecutive days; group 2, 3 and 4
were injected every other day with doxorubicin (3 mg/kg, i.p.), to obtain treatments with
cumulative doses of 6, 12, and 18 mg/kg. The fifth group was injected with L-carnitine (200
mg/kg, i.p.) for 10 consecutive days and the sixth group was received doxorubicin (18 mg/kg)
and L-carnitine (200 mg/kg). High cumulative dose of doxorubicin (18 mg/kg) significantly
increase the biochemical levels of alanine transaminase , alkaline phosphatase, total bilirubin,
total carnitine, thiobarbituric acid reactive substances (TBARs), total nitrate/nitrite (NOx) p <
0.05 and decrease in glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase
(GSHPx), glutathione-s-transferase (GST),glutathione reductase (GR) and catalase (CAT)
activity p < 0.05. The effect of doxorubicin on the activity of antioxidant genes was
confirmed by real time PCR in which the expression levels of these genes in liver tissue were
significantly decrease compared to control p < 0.05. Interestingly, L-carnitine
supplementation completely reverse the biochemical and gene expression levels induced by
doxorubicin to the control values. In conclusion, data from this study suggest that the
reduction of antioxidant defense during doxorubicin administration resulted in hepatic injury
could be prevented by L-carnitine supplementation by decreasing the oxidative stress and
preserving both the activity and gene expression level of antioxidant enzymes.
Supplemental Content
Anadolu Kardiyol Derg. 2011 Feb;11(1):3-10. doi: 10.5152/akd.2011.003. Epub 2010 Dec
24.
Protective effect of carnosine on
adriamycin-induced oxidative heart
damage in rats.
Ozdoğan K, Taşkın E, Dursun N.
Source
Department of Physiology, Faculty of Medicine, Erciyes University, Kayseri, Turkey.
Abstract
OBJECTIVE:
Oxidative stress is one of the major factors involved in the pathogenesis of adriamycin
(ADR)-induced cardiac dysfunction. The present study examined the antioxidant protective
effects of carnosine (CAR) on adriamycin-induced cardiac damage in rats.
METHODS:
Female Sprague Dawley rats were divided into four groups. Control (CONT, n=8, saline only
i.v.); carnosine (CAR, n=8.10 mg/kg/day, i.v.); adriamycin (ADR, n=10.4 mg/kg four times
every 2 days for 8 days, i.v.) alone and carnosine with adriamycin (CAR+ADR, n=10).
Carnosine was given one week before adriamycin treatment and following one week with
adriamycin treatment. After measurement of physiological functions, blood samples were
collected for biochemical assays. The hearts were excised for hemodynamic study.
Comparisons between different groups were made using ANOVA and posthoc Tukey test.
RESULTS:
Adriamycin produced evident cardiac damage revealed by; hemodynamic changes - decreased
left ventricular developed pressure (p=0.01), the maximum-minimum rates of change in left
ventricular pressure (± dP/dt, p=0.01), electrocardiogram (ECG) changes (elevated ST,
decreased R-wave, p=0.001), cardiac injury marker changes (increased creatine kinase, lactate
dehydrogenase, aspartate aminotransferase and alanine aminotransferase), plasma antioxidant
enzymes activity changes (decreased superoxide dismutase, glutathione peroxidase, catalase
activities, p=0.03) and lipid peroxidation (elevated malondialdehyde, p=0.05) to the control
and carnosine groups. Carnosine treatment caused significant attenuation (p=0.05) of cardiac
dysfunction induced by adriamycin (CAR+ADR), revealed by normalization of the
ventricular function, ECG and biochemical variables.
CONCLUSION:
An increase in oxidative stress, superoxide dismutase, glutathione peroxidase levels, catalase
inactivation and cardiac dysfunction induced by adriamycin were prevented by carnosine.
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