Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 7

gentamicin Related Abstracts

7 Protective Effect of L-Carnitine against Gentamicin-Induced Nephrotoxicity in Rats

Authors: Mohamed F. Ahmed, Mabruka S. Elashheb, Fatma M. Ben Rabha

Abstract:

This study aimed to determine the possible protective effects of L‐carnitine against gentamicin‐induced nephrotoxicity. Forty male albino rats were divided into 4 groups (10 rats each); Group 1: normal control, group 2: induced nephrotoxicity (gentamicin 50 mg/kg/day S.C; 8 days) , group 3: treated with L‐carnitine (40 mg/kg/d SC for 12 days) and group 4: treated with L‐carnitine 4 days before and for 8 days in concomitant with gentamicin. Gentamicin‐induced nephrotoxicity (group 2): caused significant increase in serum urea, creatinine, urinary N‐acetyl‐B‐D‐glucosaminidase (NAG), gamma glutamyl transpeptidase (GGT), urinary total protein and kidney tissue malondialdehyde (MDA) with significant decrease in serum superoxide dismutase (SOD), serum catalase and creatinine clearance and marked tubular necrosis in the proximal convoluted tubules with interruption in the basement membrane around the necrotic tubule compared to the normal control group. L‐carnitine 4 days before and for 8 days in concomitant with gentamicin (group 4) offered marked decrease in serum urea, serum creatinine, urinary NAG, urinary GGT, urinary proteins and kidney tissue MDA, with marked increase in serum SOD, serum catalase and creatinine clearance with marked improvement in the tubular damage compared to gentamicin‐induced nephrotoxicity group. L‐carnitine administered for 12 days produced no change in the above-mentioned parameters as compared to the normal control group. In conclusion: L‐carnitine could reduce most of the biochemical parameters and also improve the histopathological features of the kidney associated with gentamicin-induced nephrotoxicity.

Keywords: Kidney Disease, gentamicin, nephrotoxicity, L‐carnitine

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6 Effect of Green Coffee Bean Extract on Gentamicin Induced Acute Renal Failure in Rats

Authors: Amina Unis, Samah S. El Basateeny, Noha A. H. Nassef

Abstract:

Introduction: Acute Renal Failure (ARF) is one of the most common problems encountered in hospitalized critically ill patients. In recent years great effort has been focused on the introduction of herbal medicine as a novel therapeutic agent for prevention of ARF. Hence, the current study was designed to investigate the effect of Green Coffee Bean Extract (GCBE) on gentamicin induced ARF in rats. Methods: The study was conducted on 60 male rats divided into six equal groups. Group 1 served as normal control group and GCBE was administered for 7 days at a dose of 20 mg/kg/day in group 2 and 40 mg/kg/day in group 3 to test the effect of GCBE on normal kidneys. ARF was induced by a daily intraperitoneal injection of gentamicin (80 mg/kg) for 7 days in group 4 (model group), group 5 (GCBE 20 mg/kg/day) and group 6 (GCBE 20 mg/kg/day). All rats were sacrificed after 7 days and blood was withdrawn for kidney function tests. Kidneys were removed for determination of renal oxidative stress markers and histopathological examination. Results: The present study showed that rats that received oral GCBE for 7 days without induction of ARF showed no significant change in all the assessed parameters in comparison to the normal control group, while rats in the groups that received oral GCBE for 7 days with induction of ARF showed a significant improvement in kidney functions tests (decrease in serum urea, serum creatinine, and blood urea nitrogen) when compared to the ARF model group. Moreover, there was significant amelioration in renal oxidative stress markers (renal malondialdehyde, renal superoxide dismutase) and renal histopathological changes in the GCBE treated groups along induction of ARF when compared to ARF model group. The most significant improvement was reported in the group where GCBE was administered for 7 days in a dose 40 mg/kg/day, along with induction of ARF. Conclusion: GCBE has a potential role in ameliorating renal damage involved in ARF mostly through its antioxidant effect.

Keywords: pharmacology, gentamicin, green coffee bean extract, acute renal failure

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5 Fractionation of Biosynthetic Mixture of Gentamicins by Reactive Extraction

Authors: L. Kloetzer, M. Poştaru, A. I. Galaction, D. Caşcaval

Abstract:

Gentamicin is an aminoglycoside antibiotic industrially obtained by biosynthesis of Micromonospora purpurea or echinospora, the product being a complex mixture of components with very similar structures. Among them, three exhibit the most important biological activity: gentamicins C1, C1a, C2, and C2a. The separation of gentamicin from the fermentation broths at industrial scale is rather difficult and it does not allow the fractionation of the complex mixture of gentamicins in order to increase the therapeutic activity of the product. The aim of our experiments is to analyze the possibility to selectively separate the less active gentamicin, namely gentamicin C1, from the biosynthetic mixture by reactive extraction with di-(2-ethylhexyl) phosphoric acid (D2EHPA) dissolved in dichloromethane, followed selective re-extraction of the most active gentamicins C1a, C2, and C2a. The experiments on the reactive extraction of gentamicins indicated the possibility to separate selectively the gentamicin C1 from the mixture obtained by biosynthesis. The extraction selectivity is positively influenced by increasing the pH-value of an aqueous solution and by using a D2EHPA concentration in organic phase closer to the value needed for an equimolecular ratio between the extractant and this gentamicin. For quantifying the selectivity of separation, the selectivity factor, calculated as the ratio between the degree of reactive extraction of gentamicin C1 and the overall extraction degree of gentamicins were used. The possibility to remove the gentamicin C1 at an extractant concentration of 10 g l-1 and pH = 8 is presented. In these conditions, it was obtained the maximum value of the selectivity factor of 2.14, which corresponds to the modification of the gentamicin C1 concentration from 31.92% in the biosynthetic mixture to 72% in the extract. The re-extraction of gentamicins C1, C1a, C2, and C2a with sulfuric acid from the extract previously obtained by reactive extraction (mixture A – extract obtained by non-selective reactive extraction; mixture B – extract obtained by selective reactive extraction) allows for separating selectively the most active gentamicins C1a, C2, and C2a. For recovering only the active gentamicins C1a, C2, and C2a, the re-extraction must be carried out at very low acid concentrations, far below those corresponding to the stoichiometry of its chemical reactions with these gentamicins. Therefore, the mixture resulted by re-extraction contained 92.6% gentamicins C1a, C2, and C2a. By bringing together the aqueous solutions obtained by reactive extraction and re-extraction, the overall content of the active gentamicins in the final product becomes 89%, their loss reaching 0.3% related to the initial biosynthetic product.

Keywords: gentamicin, di-(2-ethylhexyl) phosphoric acid, reactive extraction, selectivity factor

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4 Pharmaceutical Equivalence of Some Injectable Gentamicin Generics Used in Veterinary Practice in Nigeria

Authors: F. A. Gberindyer, M. O.Abatan, A. B. Saba

Abstract:

Background: Gentamicin is an aminoglycoside antibiotic used in the treatment of infections caused by Gram-negative aerobic bacteria organisms in human and animals. In Nigeria, there are arrays of multisource generic versions of injectable gentamicin sulphate in the drug markets. There is a high prevalence of counterfeit and substandard drugs in the third world countries with consequent effect on their therapeutic efficacy and safety. Aim: The aim of this study was to investigate pharmaceutical equivalence of some of these generics used in veterinary practice in Nigeria. Methodology: About 20 generics of injectable gentamicin sulphate were sampled randomly across Nigeria but 15 were analyzed for identity and potency. Identity test was done using Fourier transform infra red spectroscopy and the spectral for each product compared with that of the USP reference standard for similarity. Microbiological assay using agar diffusion method with E. coli as a test organism on nutrient agar was employed and the respective diameters of bacterial inhibition zones obtained after 24 hour incubation at 37°C. The percent potency for each product was thereafter calculated and compared with the official specification. Result And Discussion: None of the generics is produced in any African country. About 75 % of the products are imported from China whereas 60 % of the veterinary generics are manufactured in Holland. Absorption spectra for the reference and test samples were similar. Percent potencies of all test products were within the official specification of 95-115 %. Nigeria relies solely on imported injectable gentamicin sulphate products. All sampled generic versions passed both identity and potency tests. Clinicians should ensure that drugs are used rationally since the converse could be contributing to the therapeutic failures reported for most of these generics. Bioequivalence study is recommended to ascertain their interchangeability when parenteral extra venous routes are indicated.

Keywords: Identity, gentamicin, generics, multisource, potency

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3 Prevalence of Antibiotic Resistant Enterococci in Treated Wastewater Effluent in Durban, South Africa and Characterization of Vancomycin and High-Level Gentamicin-Resistant Strains

Authors: S. H. Gasa, L. Singh, B. Pillay, A. O. Olaniran

Abstract:

Wastewater treatment plants (WWTPs) have been implicated as the leading reservoir for antibiotic resistant bacteria (ARB), including Enterococci spp. and antibiotic resistance genes (ARGs), worldwide. Enterococci are a group of clinically significant bacteria that have gained much attention as a result of their antibiotic resistance. They play a significant role as the principal cause of nosocomial infections and dissemination of antimicrobial resistance genes in the environment. The main objective of this study was to ascertain the role of WWTPs in Durban, South Africa as potential reservoirs for antibiotic resistant Enterococci (ARE) and their related ARGs. Furthermore, the antibiogram and resistance gene profile of Enterococci species recovered from treated wastewater effluent and receiving surface water in Durban were also investigated. Using membrane filtration technique, Enterococcus selective agar and selected antibiotics, ARE were enumerated in samples (influent, activated sludge, before chlorination and final effluent) collected from two WWTPs, as well as from upstream and downstream of the receiving surface water. Two hundred Enterococcus isolates recovered from the treated effluent and receiving surface water were identified by biochemical and PCR-based methods, and their antibiotic resistance profiles determined by the Kirby-Bauer disc diffusion assay, while PCR-based assays were used to detect the presence of resistance and virulence genes. High prevalence of ARE was obtained at both WWTPs, with values reaching a maximum of 40%. The influent and activated sludge samples contained the greatest prevalence of ARE with lower values observed in the before and after chlorination samples. Of the 44 vancomycin and high-level gentamicin-resistant isolates, 11 were identified as E. faecium, 18 as E. faecalis, 4 as E. hirae while 11 are classified as “other” Enterococci species. High-level aminoglycoside resistance for gentamicin (39%) and vancomycin (61%) was recorded in species tested. The most commonly detected virulence gene was the gelE (44%), followed by asa1 (40%), while cylA and esp were detected in only 2% of the isolates. The most prevalent aminoglycoside resistance genes were aac(6')-Ie-aph(2''), aph(3')-IIIa, and ant(6')-Ia detected in 43%, 45% and 41% of the isolates, respectively. Positive correlation was observed between resistant phenotypes to high levels of aminoglycosides and presence of all aminoglycoside resistance genes. Resistance genes for glycopeptide: vanB (37%) and vanC-1 (25%), and macrolide: ermB (11%) and ermC (54%) were detected in the isolates. These results show the need for more efficient wastewater treatment and disposal in order to prevent the release of virulent and antibiotic resistant Enterococci species and safeguard public health.

Keywords: gentamicin, antibiogram, enterococci, Vancomycin, virulence signatures

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2 Mesoporous Titania Thin Films for Gentamicin Delivery and Bone Morphogenetic Protein-2 Immobilization

Authors: Ane Escobar, Paula Angelomé, Mihaela Delcea, Marek Grzelczak, Sergio Enrique Moya

Abstract:

The antibacterial capacity of bone-anchoring implants can be improved by the use of antibiotics that can be delivered to the media after the surgery. Mesoporous films have shown great potential in drug delivery for orthopedic applications, since pore size and thickness can be tuned to produce different surface area and free volume inside the material. This work shows the synthesis of mesoporous titania films (MTF) by sol-gel chemistry and evaporation-induced self-assembly (EISA) on top of glass substrates. Pores with a diameter of 12nm were observed by Transmission Electron Microscopy (TEM). A film thickness of 100 nm was measured by Scanning Electron Microscopy (SEM). Gentamicin was used to study the antibiotic delivery from the film by means of High-performance liquid chromatography (HPLC). The Staphilococcus aureus strand was used to evaluate the effectiveness of the penicillin loaded films toward inhibiting bacterial colonization. MC3T3-E1 pre-osteoblast cell proliferation experiments proved that MTFs have a good biocompatibility and are a suitable surface for MC3T3-E1 cell proliferation. Moreover, images taken by Confocal Fluorescence Microscopy using labeled vinculin, showed good adhesion of the MC3T3-E1 cells to the MTFs, as well as complex actin filaments arrangement. In order to improve cell proliferation Bone Morphogenetic Protein-2 (BMP-2) was adsorbed on top of the mesoporous film. The deposition of the protein was proved by measurements in the contact angle, showing an increment in the hydrophobicity while the protein concentration is higher. By measuring the dehydrogenase activity in MC3T3-E1 cells cultured in dually functionalized mesoporous titatina films with gentamicin and BMP-2 is possible to find an improvement in cell proliferation. For this purpose, the absorption of a yellow-color formazan dye, product of a water-soluble salt (WST-8) reduction by the dehydrogenases, is measured. In summary, this study proves that by means of the surface modification of MTFs with proteins and loading of gentamicin is possible to achieve an antibacterial effect and a cell growth improvement.

Keywords: Biocompatibility, Antibacterial, Implants, gentamicin, osteoblasts, cell proliferation, bone morphogenetic protein-2, mesoporous titania films

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1 Development and Validation of a Liquid Chromatographic Method for the Quantification of Related Substance in Gentamicin Drug Substances

Authors: V. Murugan, Prema Kumari, Sofiqul Islam, Hari

Abstract:

Gentamicin is a broad spectrum water-soluble aminoglycoside antibiotics produced by the fermentation process of microorganism known as Micromonospora purpurea. It is widely used for the treatment of infection caused by both gram positive and gram negative bacteria. Gentamicin consists of a mixture of aminoglycoside components like C1, C1a, C2a, and C2. The molecular structure of Gentamicin and its related substances showed that it has lack of presence of chromophore group in the molecule due to which the detection of such components were quite critical and challenging. In this study, a simple Reversed Phase-High Performance Liquid Chromatographic (RP-HPLC) method using ultraviolet (UV) detector was developed and validated for quantification of the related substances present in Gentamicin drug substances. The method was achieved by using Thermo Scientific Hypersil Gold analytical column (150 x 4.6 mm, 5 µm particle size) with isocratic elution composed of methanol: water: glacial acetic acid: sodium hexane sulfonate in the ratio 70:25:5:3 % v/v/v/w as a mobile phase at a flow rate of 0.5 mL/min, column temperature was maintained at 30 °C and detection wavelength of 330 nm. The four components of Gentamicin namely Gentamicin C1, C1a, C2a, and C2 were well separated along with the related substance present in Gentamicin. The Limit of Quantification (LOQ) values were found to be at 0.0075 mg/mL. The accuracy of the method was quite satisfactory in which the % recovery was resulted between 95-105% for the related substances. The correlation coefficient (≥ 0.995) shows the linearity response against concentration over the range of Limit of Quantification (LOQ). Precision studies showed the % Relative Standard Deviation (RSD) values less than 5% for its related substance. The method was validated in accordance with the International Conference of Harmonization (ICH) guideline with various parameters like system suitability, specificity, precision, linearity, accuracy, limit of quantification, and robustness. This proposed method was easy and suitable for use for the quantification of related substances in routine analysis of Gentamicin formulations.

Keywords: Ultraviolet, gentamicin, high performance liquid chromatography, reversed phase-high performance liquid chromatographic (RP-HPLC), isocratic

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