Therapeutic potential of salidroside in preserving rat cochlea organ of corti from gentamicin-induced injury through modulation of NRF2 signaling and GSK3ß/NF-κB pathway.

Salidroside (SAL) is a phenol glycoside compound found in plants of the Rhodiola genus which has natural antioxidant and free radical scavenging properties. SAL are able to protect against manganese-induced ototoxicity. However, the molecular mechanism by which SAL reduces levels of reactive oxygen species (ROS) is unclear. Here, we established an in vitro gentamicin (GM) ototoxicity model to observe the protective effect of SAL on GM-induced hair cells (HC) damage. Cochlear explants of postnatal day 4 rats were obtained and randomly divided into six groups: two model groups (treatment with 0.2 mM or 0.4 mM GM for 24 h); two 400 µmol/L SAL-pretreated groups pretreatment with SAL for 3 h followed by GM treatment (0.2 mM or 0.4 mM) for 24 h; 400 µmol/L SAL group (treatment with SAL for 24 h); control group (normal cultured cochlear explants). The protective effects of SAL on GM-induced HC damage, and on mRNA and protein levels of antioxidant enzymes were observed. HC loss occurred after 24 h of GM treatment. Pretreatment with SAL significantly reduced GM-induced OHC loss. In cochlear tissues, mRNA and protein levels of NRF2 and HO-1 were enhanced in the GM alone group compared with the SAL pretreatment GM treatment group. SAL may protect against GM-induced ototoxicity by regulating the antioxidant defense system of cochlear tissues; SAL can activate NRF2/HO-1 signaling, inhibit NF-κB activation, activate AKT, and increase inhibitory phosphorylation of GSK3ß to decrease GSK3 activity, all of which exert antioxidant effects.

The Nephroprotective Effect of Cornelian Cherry (Cornus mas L.) and Rowanberry (Sorbus aucuparia L.) in Gentamicin-Induced Nephrotoxicity on Wistar Rats with Emphasis on the Evaluation of Novel Renal Biomarkers and the Antioxidant Capacity in Correlation with Nitro-Oxidative Stress.

In spite of its well-known nephrotoxicity, gentamicin is nonetheless routinely used in humans and animals. However, no adjuvant treatments have been implemented to mitigate this harmful effect. Given this concern, medicinal plants represent a significant reservoir of natural antioxidants that could potentially reduce the renal oxidative stress induced by gentamicin. Therefore, the main objective of this research was to investigate the nephroprotective properties of Cornus mas and Sorbus aucuparia fruits in an experimental model of nephrotoxicity. The 3-week study was performed on male Wistar rats, which were randomly divided into six experimental groups, being subcutaneously treated with 50 mg/kg gentamicin and orally given Cornus mas and Sorbus aucuparia extracts, in doses of 40 mg/kg and 10 mg/kg, respectively. Antioxidant therapy significantly improved the nitro-oxidative stress parameters as well as the specific renal biomarkers KIM-1 and iNAG, demonstrating a considerable renal tubular protective impact. These outcomes were reinforced by biochemical and histopathological enhancements. Nevertheless, neither of the tested extracts succeeded in substantially diminishing BUN levels. Additionally, CysC did not significantly decline following extracts treatment, suggesting that the remedies did not effectively protect renal glomeruli against gentamicin stress. Future studies are required in order to determine the underlying mechanisms of these berries.

Protective effect of ethanolic extract of Elettaria Cardamomum against gentamicin hepato-renal toxicity in male albino rats.

OBJECTIVE: Cardamom is one of the spices containing a wide range of antioxidants and is used in medicinal preparations. Thus, in this study, we want to explore the protective effect of ethanolic cardamom extract on the liver-kidney toxicity caused by gentamicin in male albino rats. MATERIALS AND METHODS: The experiment was applied to twenty-eight male albino rats divided randomly into four groups. The control group was given 1 ml/kg of saline orally. The gentamicin (GM) group was given a daily 80 mg/kg i.p of GM for seven days. Another group was given 100 or 200 mg/kg b.wt. p.o. ethanolic extract of Elettaria Cardamomum (EC) for seven days. Blood and liver-kidney samples were taken after the end of the study for analyses to test for liver-kidney function and lipid profile (LP). RESULTS: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin activities were higher in the GM group than in the control group. However, the groups' differences in globulin levels and total protein (TP) were not statistically significant. Compared to the control group, the albumin level in the gentamicin group was considerably lower. On the other hand, creatinine and urea levels, lipid, serum total cholesterol levels, and high-density lipoprotein (HDL) significantly increased in the gentamicin group but decreased in the control group and co-treated groups with gentamicin and ethanolic extract EC. Low-density lipoprotein (LDL) significantly dropped, while the control group showed high levels of lipid and serum total cholesterol. CONCLUSIONS: EC ethanolic extract shields the liver-kidney against GM harmful effects in male rats. Recent research demonstrated that the effects of the plant cardamom were the same at both low-high doses. The phenolic elements in EC may be responsible for this protective effect.

Potential Protective Effects of Ruta Chalepensis L. Extracts Against Gentamicin-Induced Nephrotoxicity via Reduction on Apoptotic, DNA Damage and Oxidative Stress Markers in Mice.

In this study, the protective effects of Ruta chalepensis L. extracts on the extent of tissue damage in gentamicin-induced nephrotoxicity have been investigated. Ruta chalepensis L. extracts were prepared by subcritical water and ultrasound-assisted organic solvent extraction methods. Protective activity of Ruta chalepensis L. extracts on Gentamicin-induced nephrotoxicity is investigated by apoptotic, DNA damage, oxidative stress markers and evaluating histopathological in kidney tissue of mice. Gentamicin significantly increased Caspase-3 and -8 activities, NO levels, serum creatinine and BUN, while 8-OHdG and MDA levels were significantly decreased with Ruta chalepensis L. extract treatment. In addition, Ruta chalepensis L. extracts treatment significantly increased CAT and SOD activities. Histopathological alterations in Gentamicin group were significantly diminished by application of Ruta chalepensis L. extracts. These results suggest that treatment with Ruta chalepensis L. extracts may ameliorate renal dysfunction and structural damage through the reduction of oxidative stress and apoptosis in the kidney.

Protective effects of nigella sativa oil against gentamicin-induced ototoxicity in rats: A dose-ranging study.

OBJECTIVE: Aminoglycosides are relatively potent antibiotics used against some life-threatening infections but contribute to ototoxicity. Although the beneficial effects of high-dose nigella sativa oil (NSO) on ototoxicity in the form of intratympanic or oral use have been demonstrated, no variable-dose studies have been conducted on this subject. We aimed to investigate the potential protective effect of different doses of intraperitoneal (i.p.) NSO on Gentamicin (GM)-induced ototoxicity with auditory brainstem responses (ABR) testing. METHODS: Thirty adult male Sprague-Dawley rats (300-400 gr) were used in this study. Rats were randomly divided into 5 groups, with six animals in each group: All the groups received GM (120 mg/kg i.p) for ten days. Group 1: 0.9% saline solution (0.3 ml/kg i.p.), Group 2: NSOL (low dose 0.1 ml/kg i.p.), Group 3: NSOM (median dose 0.3 ml/kg i.p.), Group 4: NSOH (high dose 3 ml/kg i.p.), Group 5: NSOML (late onset median dose 0.3 ml/kg i.p) were given for fifteen days. But death occurred in 3 rats in group 4 and they were excluded from the study. The pretreatment and posttreatment ABR testings were performed. RESULTS: The posttreatment ABR results were compared with the pretreatment values. A significant difference was found in group 1 (p:0,002), group 2 (p: 0,040), and group 4 (p: 0,027). When the posttreatment tests were compared with each other, there was a significant difference between groups 1 and 2 (p < 0,001), groups 1 and 3 (p < 0,001), and groups 1 and 5 (p < 0,001). CONCLUSIONS: The administration of 0.1 ml/kg and 3 ml/kg dose of NSO does not prevent ototoxicity. The 0.3 ml/kg dose of NSO effectively prevents GM-induced ototoxicity within both prophylactic and therapeutic use.

Treatment options for neonatal infections in the post-cefotaxime era.

INTRODUCTION: Cefotaxime has been used for the management of neonatal infections since the 1990s for suspected meningitis and to mitigate gentamicin-associated renal injury. Its shortage in 2015 and subsequent removal from the U.S. pharmaceutical market forced providers to consider alternatives. Ceftriaxone, a cephalosporin with an identical antibacterial spectrum of activity to cefotaxime, is contraindicated in neonates due to its risk of biliary pseudolithiasis. Ceftazidime was recommended as an alternative by the American Academy of Pediatrics but is inequivalent. AREAS COVERED: This article addresses indications for cephalosporin use and considerations when selecting an alternative to cefotaxime. Differences among cefotaxime, ceftriaxone, ceftazidime, and cefepime are discussed and compared to the standard-of-care presumptive regimen, ampicillin, and gentamicin. The authors consider the data behind the neonatal contraindication to ceftriaxone and provide recommendations for their application to practice. EXPERT OPINION: The data against ceftriaxone use in neonates remain poor, particularly in the context of the cefotaxime shortage and lack of an equivalent alternative. Ceftriaxone could be considered in low-risk neonates without hyperbilirubinemia or exposure to calcium-containing fluids on a case-by-case basis. Ceftazidime monotherapy for presumptive management of neonatal infections is inappropriate; cefepime should be more frequently utilized in neonates who are poor candidates for ceftriaxone.

Nephroprotective effects of Helianthus annuus seeds extract in gentamicin induced nephrotoxic male mice.

Acute kidney injury (AKI) causes a decrease in renal function which leads to failure in balancing electrolyte, fluid and acid-base homoeostasis. AKI is a damaging and life-threatening disorder, but it can be managed if identified earlier. This study aimed to investigate the possible nephroprotective effect of Helianthus annuus seeds extract against gentamicin (GM) induced nephrotoxicity in male mice. The control group (0.5 ml normal saline i.p.,), Gentamycin (GM) group (GM 100 mg/kg i.p), silymarin + GM group (silymarin 50 mg/kg and GM 100 mg/kg i.p.,), H. annuus extract (HAE) and GM, group (HAE 250 mg/kg and GM 100 mg/kg i.p), HAE2 + GM group (HAE2; 500 mg/kg and GM 100 mg/kg i.p) and H. annuus oil (HAO) + GM (HAO 2.5 ml/kg and GM 100 mg/kg i.p). Serum creatinine, urea and blood urea nitrogen (BUN) were significantly (P< 0.001) elevated in the GM group compared to the control group. The elevated level of serum creatinine, urea and BUN were decreased significantly (P<0.001) in groups treated with HAE and HAO extracts compared to the GM group. The kidney histopathological study from the GM group showed tubular necrosis, vacuolation and fibrosis. However, the animal that received HAE and HAO showed no tubular necrosis and vacuolation. Only mild inflammation was observed compared to the GM group. In conclusion, the extract caused marked radical scavenger and protected the kidney from oxidative damage of GM. H. annuus seeds contain strong antioxidant compounds, including flavonoids, phenolic acids, tocopherols and minerals, which could be responsible for the current show.

Effect of Hydroaloholic Extract of Rotula Aquatica Lour on Gentamicin-Induced Nephrotoxicity in Wistar Albino Rats: An In Vitro and In Vivo Approach.

One-third of the world population suffer from kidney complications such as acute and chronic renal failure, renal calculi, kidney stones, Fanconi's syndrome and urethritis which doesn't have a proper effective treatment regimen. The current study explores the nephroprotective effect of herbal drug Rotula Aquatica by both In Vitro and In Vivo methods. MTT assay was applied In Vitro to evaluate the nephroprotective effect of R. aquatica leaves extract on HEK 293 cell line. The acute toxicity of the extract was evaluated as per the limit test under the protocol of OECD 423 at a concentration of 2000 mg/kg using 6 female rats. Further, an In Vivo study using the Gentamicin-instigated nephrotoxicity model was carried out for a period of 8 days. Biochemical markers of renal damage, endogenous antioxidants and histopathology were determined to assess the effect of treatment. The In Vitro study using HEK 293 cell line resulted in an EC50 value of 51.50 µg/ml for the extract in comparison to the standard drug Cytsone (12.26 µg/ml). Based on the limit test of OECD 423, doses of 200 and 400 mg/kg were chosen for the study. The results revealed a strong nephroprotective activity at 400 mg/kg in Gentamicin-induced nephrotoxicity against standard drug cystone by restoring the decrement in body weight, renal enzymatic and non-enzymatic antioxidants, creatinine and urea levels in urine and plasma. This indicated that hydroalcoholic extract of Rotula aquatica (HAERA) can prevent the Gentamicin toxicity due to the high content of antioxidant and anti-inflammatory secondary metabolites.

Protective and Curative Effects of Ethanol extract of Tinospora Cordifolia on Gentamicin-induced Nephrotoxicity in Rats.

Gentamicin induced acute tubular necrosis (ATN) in intrinsic variety of acute renal failure (ARF) results from oxidative stress leading to cellular lipid peroxidation. Tinospora cordifolia (Tc), locally named as 'Guluncha' is an herbal plant with medicinal value possess antioxidant property as well as significant scavenging activity in different extracts and easily available in Bangladesh. This prospective study was approved by the Institutional Review Board of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. This study was conducted to assess the effect of ethanol extract of Tc on gentamicin induced renal damage in rats in the department of Pharmacology, BSMMU, Dhaka, Bangladesh from January 2014 to June 2014. For this purpose, sixty rats were divided into six equal groups. Gentamicin (80mg/kg/day, 7 days) was administered and nephrotoxicity was evaluated biochemically by estimating elevated levels of serum creatinine and serum urea. Extant of lipid peroxidation was assessed by estimating renal cortical malondialdehyde (MDA) levels. The ethanol extract of Tc (200mg/kg/day) was administered with gentamicin concurrently and also consecutively to detect preventive and curative effects respectively. Statistically significant amelioration in the biochemical parameters both in serum and renal tissue suggested that active compound or compounds extracted from Tinospora cordifolia have both protective and curative effects against nephrotoxicity, though responsible active ingredient, accurate mechanism or safety profile was not confirmed by this study.

Green coffee bean extract attenuates gentamicin induced acute nephrotoxicity in rats / El extracto de grano de café verde atenúa la nefrotoxicidad aguda inducida por gentamicina en ratas

Gentamicin induced acute nephrotoxicity (GIAN) is considered as one of the important causes of acute renal failure. In recent years' great effort has been focused on the introduction of herbal medicine as a novel therapeutic agent for prevention of GIAN. Hence, the current study was designed to investigate the effect of green coffee bean extract (GCBE) on GIAN in rats. Results of the present study showed that rat groups that received oral GCBE for 7 days after induction of GIAN(by a daily intraperitoneal injection of gentamicin for 7days), reported a significant improvement in renal functions tests when compared to the GIAN model groups. Moreover, there was significant amelioration in renal oxidative stress markers (renal malondialdehyde, renal superoxide dismutase) and renal histopathological changes in the GCBE-treated groups when compared to GIAN model group. These results indicate that GCBE has a potential role in ameliorating renal damage involved in GIAN.

La nefrotoxicidad aguda inducida por gentamicina (GIAN) se considera una de las causas importantes de insuficiencia renal aguda. En los últimos años, el gran esfuerzo se ha centrado en la introducción de la medicina herbal como un nuevo agente terapéutico para la prevención de GIAN. Por lo tanto, el estudio actual fue diseñado para investigar el efecto del extracto de grano de café verde (GCBE) sobre la GIAN en ratas. Los resultados del presente estudio mostraron que los grupos de ratas que recibieron GCBE oral durante 7 días después de la inducción de GIAN (mediante una inyección intraperitoneal diaria de gentamicina durante 7 días), informaron una mejora significativa en las pruebas de función renal en comparación con los grupos del modelo GIAN. Además, hubo una mejora significativa en los marcadores de estrés oxidativo renal (malondialdehído renal, superóxido dismutasa renal) y cambios histopatológicos renales en los grupos tratados con GCBE en comparación con el grupo del modelo GIAN. Estos resultados indican que GCBE tiene un papel potencial en la mejora del daño renal involucrado en GIAN.

Curcumin protects rats against gentamicin-induced nephrotoxicity by amelioration of oxidative stress, endoplasmic reticulum stress and apoptosis.

CONTEXT: Gentamicin (GM) is an aminoglycoside antibiotic which is commonly used against Gram-negative bacterial infection; however, serious complications including nephrotoxicity could limit its clinical use. OBJECTIVE: The present study examined the protective effects of curcumin (CUR) on endoplasmic reticulum (ER) stress-mediated apoptosis through its antioxidative property in GM-induced nephrotoxicity in rats. MATERIALS AND METHODS: Male Sprague-Dawley rats (n = 3) were divided into six groups to receive normal saline (control), GM (100 mg/kg/day), co-treatment with GM and CUR (100, 200 and 300 mg/kg/day) and CUR (200 mg/kg/day) alone for 15 days by gavage feeding. Then, the renal function, kidney injury as well as oxidative stress, antioxidative markers and ER stress-mediated apoptosis were evaluated. RESULTS: Pre-treatment of CUR rescued the nephrotoxicity in GM-treated rats. Several nephrotoxicity hallmarks were reversed in the CUR-pre-treatment group. At the dose of 200 mg/kg/day, it could significantly lower serum creatinine (from 0.95 to 0.50 mg/dL), blood urea nitrogen (from 35.00 to 23.50 mg/dL) and augmented creatinine clearance (from 0.83 to 1.71 mL/min). The normalized expression of oxidative stress marker, malondialdehyde was decreased (from 13.00 to 5.98) in line with the increase of antioxidant molecules including superoxide dismutase (from 5.59 to 14.24) and glutathione (from 5.22 to 12.53). Furthermore, the renal ER stress and apoptotic protein biomarkers were lowered in CUR treatment. DISCUSSION AND CONCLUSIONS: Our findings pave the way for the application of CUR as a supplement in the prevention of nephrotoxicity and other kidney diseases in the future.

The comparison of the effect of Origanum vulgare L. extract and vitamin C on the gentamycin-induced nephrotoxicity in rats.

The gentamicin renal toxicity has been the focal point for much discussion. The objective of this study was to investigate the impacts of Origanum vulgare L. extract and vitamin C on gentamicin dose-dependent toxicity in rats' kidney. The present study was conducted on 60 male Wistar rats divided into ten experimental groups: control (untreated), G1, G2, G3 (100, 200, 300 mg/kg gentamicin), M1, M2 and M3 (500 mg/kg marjoram extract) + 100, 200 and 300 gentamicin, V1, V2 and V3 (Vitamin C 500 mg/kg) + 100, 200 and 300 of gentamicin. On the last day, the serum was separated from heart blood and the kidney tissues were extracted to measure the biochemical and oxidative stress parameters and histological changes. Kidney damage was confirmed as dose-dependent gentamicin by biochemical and pathological parameters. Urea, Blood Urea Nitrogen (BUN), and creatinine showed a significant increase in the G3 group compared to the control, M1, and V1 groups (p < 0.01). Catalase (CAT), Glutathione peroxidase (GPx), and Superoxide dismutase (SOD) showed a significant reduction in renal tissue in the G3 group compared to the other groups (p < 0.001). Malondialdehyde (MDA) concentration in the kidney tissue of the G3 group also showed a significant increase compared to other groups (p < 0.001). Furthermore, TNFα and IL-1 levels were the highest in the G3 group, and serum total antioxidant capacity (TAC) concentration had the lowest amount compared to other groups. Moreover, histopathological lesions of the kidney showed significant statistical differences among the groups that received gentamicin with the control and M1 group. Marjoram extract at the dose of 500 mg/kg had a desirable effect on controlling gentamicin damage in the kidneys compared with vitamin C. In particular, controlling gentamicin-induced oxidative stress and inflammation by the consumption of marjoram extract and vitamin C plays an important role in protecting the kidneys.

Glutamine alleviates the renal dysfunction associated with gentamicin-induced acute kidney injury in Sprague-Dawley rats.

Sepsis is a clinical condition caused by an uncontrolled response to an infection, leading to acute kidney injury (AKI) and an increased risk of mortality. Although life support and antibiotic therapy are available, the mortality rate remains high in patients with sepsis. The present study investigated the therapeutic effect of glutamine on gentamicin-induced acute kidney injury in Sprague-Dawley rats. We randomly grouped 24 male rats to the normal control, AKI (control), glutamine 50 mg/kg, and glutamine 500 mg/kg groups. The dose was administered orally for 14 consecutive days. Rats treated with glutamine 500 mg/kg showed changes in systolic blood pressure. Glutamine increased renal blood flow, creatinine clearance, and the levels of potassium, creatinine, blood urea nitrogen, and urine osmolality, while reducing the relative excretion of sodium, potassium, urinary sodium, and plasma blood urea nitrogen and creatinine levels. In our study, glutamine supplementation reduced gentamicin-induced oxidative stress and increased catalase, superoxide dismutase, glutathione peroxidase, and glutathione levels in AKI rats. In addition, glutamine supplementation attenuated the severity of pathological features in this model. Collectively, our results showed that gentamicin has therapeutic potential against gentamicin-induced AKI due to its ability to mitigate the effects of oxidative stress.

Acupuncture Attenuates Ototoxicity Induced by Gentamicin in Mice.

CONTEXT: Presbycusis is age-related, progressive, and symmetrical hearing loss in both ears. Acupuncture can play a vital role in the diagnosis and treatment of deafness, but its functional mechanism is still not entirely clear. OBJECTIVE: The study intended to explore acupuncture's protective effects and mechanism of treatment in addressing ototoxicity induced by gentamicin (GM) in aged mice. DESIGN: The research team designed an animal study, and a mouse model of ototoxicity induced by GM was established. SETTING: The study took place in Nanchong Central Hospital, Sichuan, China. ANIMALS: The animals were 48 male, Kunming mice, with sixteen being three months old and 32 being 18 month old. INTERVENTION: The three-month-old mice were randomly assigned to a control group (n = 8) and a GM group (n = 8). The 18-month-old mice were randomly divided into four groups with eight mice each: a positive control group; a negative control group, the GM group; and two intervention groups, the acupuncture + GM group and the drug + GM group. The GM groups were intraperitoneally injected with 100 mg/kg daily of GM for 10 consecutive days. The acupuncture + GM group received acupuncture, and the drug + GM group was injected intraperitoneally with Genadol. OUTCOME MEASURES: The effects of GM induction and treatment with acupuncture or a drug on the numbers of auditory cochlear hair cells were evaluated via an auditory test and cell staining. A real-time polymerase chain reaction (PCR) was performed for gene detection. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) were measured. RESULTS: The aged mice were susceptible to GM ototoxicity. After acupuncture, the threshold of the auditory brainstem response and the number of cochlear hair cells increased significantly. Acupuncture inhibited oxidative stress via the nuclear factor erythroid-derived factor 2-related factor 2 (NRF2) signaling pathway in the mice. CONCLUSIONS: The data demonstrated that acupuncture can alleviate GM ototoxicity via the NRF2 signaling pathway, providing important support for acupuncture in treatment of GM ototoxicity.

Protective role of salicylic acid in gentamicin induced nephrotoxicity.

Salicylic acid, a phenolic compound, found in plants, possesses free radical scavenging and iron chelation properties. The present study is designed to study the antioxidant effect of salicylic acid in gentamicin induced nephrotoxicity in rabbits. For this purpose twenty four male albino rabbits were divided into 4 groups (n=6); control group, healthy untreated rabbits, gentamicin group, received only gentamicin (80mg/kg), gentamicin + salicylic acid group, received gentamicin (80mg/kg) + salicylic acid (80mg/kg) and salicylic acid group, received only salicylic acid (80mg/kg) via intra peritoneal route for 21 consecutive days. Biochemical evaluation was carried out by assessment of body weights and by estimating renal function tests (plasma urea, plasma creatinine and plasma uric acid), tissue antioxidant enzymes (catalase, SOD) and MDA level. Gentamicin induction resulted in decreased body weights, increased plasma urea, plasma creatinine, plasma uric acid, tissue MDA level and decreased tissue SOD and tissue catalase activity in gentamicin treated group which was restored by supplementation with salicylic acid in gentamicin + salicylic acid group. Our data suggests that supplementation of salicylic acid can be useful in reducing gentamicin induced nephrotoxicity in rabbits.

Effect of salicylic acid supplementation on blood glucose, lipid profile and electrolyte homeostasis in gentamicin sulphate induced nephrotoxicity.

This study was designed to investigate effect of salicylic acid supplementation in gentamicin- induced nephrotoxicity. For this purpose, twenty four male albino rabbits were divided into 4 groups (n=6); control group, healthy untreated rabbits; gentamicin group, received only gentamicin (80mg/kg); gentamicin + salicylic acid group, received gentamicin (80mg/kg) + salicylic acid (80mg/kg) and salicylic acid group, received only salicylic acid (80mg/kg) through intra peritoneal route for 21 consecutive days. Biochemical evaluation was carried out by assessment of body weights and by estimating plasma glucose, lipid profile and electrolyte homeostasis. Gentamicin sulphate induction resulted in increased plasma glucose, plasma TG, plasma cholesterol, plasma LDL, and plasma sodium and in decreased plasma HDL and plasma potassium with significant reduction in body weights in GS-treated group, which were restored by supplementation with salicylic acid in GS+SA treated group. Therefore, these findings confirm the protective role of salicylic acid in gentamicin- induced nephrotoxicity in rabbits.

Protective Effect of Opuntia dillenii (Ker Gawl.) Haw. Seed Oil on Gentamicin-Induced Nephrotoxicity: A Biochemical and Histological Analysis.

Opuntia dillenii is a medicinal plant with frequent usage in folk medicine to treat many illnesses. The present study aims to investigate the protective effect of Opuntia dillenii seed oil against gentamicin-induced nephrotoxicity in rats. The animals (rats) were randomly divided into three groups (i) the normal control group treated only with distilled water (10 mL/kg), (ii) the gentamicin group treated with distilled water (10 mL/kg) and received an intraperitoneal injection of gentamicin (80 mg/kg), and (iii) the group treated with the Opuntia dillenii seed oil (2 mL/kg) and also received an intraperitoneal injection of gentamicin (80 mg/kg). The rats received their following treatments for 14 consecutive days orally. Serum urea, creatinine, gamma-glutamyl transferase, albumin, and electrolyte levels were quantified as the markers of acute renal and liver failure. Besides, the kidney and liver relative weight, kidney malondialdehydes, and kidney histological analysis were determined. The results have shown that daily pretreatment with Opuntia dillenii seed oil (2 mL/kg) prevented severe alterations of biochemical parameters and disruptions of kidney tissue structures. In addition, the results of the present study showed for the first time that Opuntia dillenii seed oil reduced renal toxicity in gentamicin-induced nephrotoxicity in rats. Therefore, Opuntia dillenii seed oil may represent a new therapeutic avenue to preserve and protect renal function in gentamicin-treated patients.

Effects of Moringa Extract on Aminoglycoside-Induced Hair Cell Death and Organ of Corti Damage.

HYPOTHESIS: Moringa extract, a naturally occurring anti-oxidant, protects against aminoglycoside-induced hair cell death and hearing loss within the organ of Corti. BACKGROUND: Reactive oxygen species (ROS) arise primarily in the mitochondria and have been implicated in aminoglycoside-induced ototoxicity. Mitochondrial dysfunction results in loss of membrane potential, release of caspases, and cell apoptosis. Moringa extract has not previously been examined as a protective agent for aminoglycoside-induced ototoxicity. METHODS: Putative otoprotective effects of moringa extract were investigated in an organotypic model using murine organ of Corti explants subjected to gentamicin-induced ototoxicity. Assays evaluated hair cell loss, cytochrome oxidase expression, mitochondrial membrane potential integrity, and caspase activity. RESULTS: In vitro application of moringa conferred significant protection from gentamicin-induced hair cell loss at dosages from 25 to 300 µg/mL, with dosages above 100 µg/mL conferring near complete protection. Assays demonstrated moringa extract suppression of ROS, preservation of cytochrome oxidase activity, and reduction in caspase production. CONCLUSION: Moringa extract demonstrated potent antioxidant properties with significant protection against gentamicin ototoxicity in cochlear explants.

HPLC-ESI/MS profiling, phytoconstituent isolation and evaluation of renal function, oxidative stress and inflammation in gentamicin-induced nephrotoxicity in rats of Ficus spragueana Mildbr. & Burret.

Ficus spragueana Mildbr. & Burret (family Moraceae) was reported to have various biological activities. However, its activity in treatment of renal injury has not been investigated yet. The current study aimed to evaluate the effects of F. spragueana leaf extract on nephrotoxicity caused by gentamicin. Gentamicin is an important broad-spectrum antibiotic; nevertheless, it exhibits serious nephrotoxic adverse effects. HPLC-ESI/MS spectrometric analysis of the extract revealed the presence of 37 phenolic compounds. Moreover, five compounds were isolated from the leaf extract, and identified on the basis of spectroscopic analysis. The isolated compounds were syringic acid (1), p-coumaric acid (2), 3',5' O-dicaffeoylquinic acid (3), luteolin-8-C-ß-D glucopyranoside (orientin) (4) and 8-methoxy kaempferol-3-O-[α-L-rhamnopyranosyl (1→2) ß-D-glucopyranoside] (5). The gentamicin-induced nephrotoxicity model was used to evaluate the protective effect of F. spragueana on renal toxicity biomarkers throughout the development of acute kidney injury. Administration of extract led to improvement in kidney function through inhibition of kidney injury molecule-1, creatinine, blood urea nitrogen and total bilirubin, as well as decreasing the inflammatory markers interlukin1-beta and myeloperoxidase. Furthermore, it reduced the oxidative stress by increasing reduced glutathione and total antioxidant capacity levels while decreasing malondialdehyde and nitric oxide content, and improved renal histopathological injuries.

Nephroprotective potential of Anogeissus latifolia Roxb. (Dhava) against gentamicin-induced nephrotoxicity in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Stem bark of Anogeissus latifolia Roxb. (Family: Combretaceae) is used traditionally and ethnomedicinally for correction of kidney disorders. AIM OF THE STUDY: The present study demonstrates the nephroprotective potential of stem bark of A. latifolia Roxb. MATERIALS AND METHODS: The HPTLC fingerprint and HPLC analysis were carried out to standardize the ethanolic extract of stem bark of A. latifolia (ALEE) using ellagic acid as a marker. Nephrotoxicity was induced in adult Wistar albino rats by gentamicin (100 mg/kg, intraperitoneally for 8 days) and they were treated with ALEE (100, 200 and 400 mg/kg, orally for 8 days), ellagic acid (10 mg/kg, orally for 8 days) and cystone syrup (5 ml/kg, orally), a standard reference a polyherbal formulation. Urine volume, serum and urine levels of creatinine, urea and uric acid, oxidative stress parameters (lipid peroxidation, catalase, superoxide dismutase and reduced glutathione), inflammatory markers (TNF-α and IL-6) and kidney weight along with its histological changes were studied in experimental animals. RESULTS: HPTLC, HPLC and LC-MS analysis of ALEE revealed the presence of ellagic acid and other various phytoconstituents. Administration of gentamicin caused significant increase in urine output and kidney weight, elevated biochemical, inflammatory and oxidative stress parameters as well as caused histological damage in the kidney tissue. These parameters were attenuated by the concurrent treatment with ALEE and ellagic acid. The effects were comparable to cystone. CONCLUSION: Present investigations concluded that ALEE exhibited nephroprotective potential and validated the traditional use of stem bark of A. latifolia in kidney disorders. The nephroprotective effect may be attributed to the antioxidant and anti-inflammatory phytoconstituents in ALEE.