Talib Hussain

Evaluation of antihepatotoxic potential of Solanum xanthocarpum fruit extract against antitubercular drugs induced hepatopathy in experimental rodents.

OBJECTIVE To assess the hepatoprotective effect of Solanum xanthocarpum (S. xanthocarpum) fruit extract against antitubercular drug-induced liver toxicity in experimental animals. METHODS Ethanolic (50%) fruit extract of S. xanthocarpum (100, 200 and 400 mg/kg bw) was administered daily for 35 days in experimental animals. Liver toxicity was induced by combination of three antitubercular drugs [isoniazid (I) 7.5 mg/kg, rifampicin (R) 10 mg/kg and pyrazinamide (P) 35 mg/kg] given orally as suspension for 35 days in rats. The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatise (ALP), total bilirubin (TBL), albumin (ALB), total protein (TP), lactate dehydroginase (LDH), and serum cholesterol (CHL). Meanwhile, in vivo antioxidant activities as lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were measured in rat liver homogenate. The biochemical observations were supplemented by histopathological examination. RESULTS The results demonstrated that treatment with S. xanthocarpum significantly (P<0.05-P<0.001) and dose-dependently prevented drug induced increase in serum levels of hepatic enzymes. Furthermore, S. xanthocarpum significantly (up to P<0.001) reduced the LPO in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and CAT towards normal levels. Histopathology of the liver tissue showed that S. xanthocarpum attenuated the hepatocellular necrosis and led to reduction in inflammatory cells infiltration. CONCLUSIONS The results of this study strongly indicate the protective effect of S. xanthocarpum against liver injury which may be attributed to its hepatoprotective activity, and thereby scientifically support its traditional use.

Acute and subacute oral toxicity evaluation of Tephrosia purpurea extract in rodents

Abstract Objective To evaluate the acute and subacute toxicity of 50% ethanolic extract of Tephrosia purpurea (T. purpurea) in rodents. Methods The acute toxicity test was conducted in Swiss albino mice. The extract of T. purpurea was administrated in single doses of 50, 300 and 2000 mg/kg and observed for behavioral changes and mortality, if any. In subacute toxicity study, Wistar rats of either sex were administered two doses of T. purpurea i.e., 200 and 400 mg/kg (One-tenth and one-fifth of the maximum tolerated dose), p.o. for 4 weeks. During 28 days of treatment, rats were observed weekly for any change in their body weight, food and water intake. At the end of 28 days, rats were sacrificed for hematological, biochemical and histopathology study. Results In the acute toxicity study, T. purpurea was found to be well tolerated upto 2000 mg/kg, produced neither mortality nor changes in behavior in mice. In subacute toxicity study, T. purpurea at dose level of 200 and 400 mg/kg did not produce any significant difference in their body weight, food and water intake when compared to vehicle treated rats. It also showed no significant alteration in hematological and biochemical parameters in experimental groups of rats apart from a decrease in aspartate transaminase, alanine transaminase and alkaline phosphate content at the dose of 400 mg/kg. Histopathological study revealed normal architecture of kidney and liver of T. purpurea treated rats. Conclusions These results demonstrated that there is a wide margin of safety for the therapeutic use of T. purpurea and further corroborated the traditional use of this extract as an anti hepatocarcinogenic agent.

Nephroprotective activity of Solanum xanthocarpum fruit extract against gentamicin-induced nephrotoxicity and renal dysfunction in experimental rodents.

OBJECTIVE To evaluate nephroprotective potential of Solanum xanthocarpum (S. xanthocarpum) fruit extract(SXE) against gentamicin (GM) induced nephrotoxicity and renal dysfunction. METHODS Twenty-four Wistar rats were divided into four groups (n=6). Control rats that received normal saline (i.p.) and 0.5% carboxymethyl cellulose (p.o.) per day for 8 d. Nephrotoxicity was induced in rats by intraperitoneal administration of GM (100 mg/kg/d for 8 d) and were treated with SXE (200 and 400 mg/kg/d (p.o.) for 8 d). Plasma and urine urea and creatinine, kidney weight, urine output, blood urea nitrogen, renal enzymatic and non-enzymatic antioxidants and lipid peroxidation was evaluated along with histopathological investigation in various experimental groups of rats. RESULTS It was observed that the GM treatment induced significant elevation (P<0.001) in plasma and urine urea, creatinine, kidney weight, blood urea nitrogen, renal lipid peroxidation along with significant decrement (P<0.001) in urine output, renal enzymatic and non-enzymatic antioxidants. SXE 200 and 400 mg/kg treatment to GM treated rats recorded significant decrement (up to P<0.001) in plasma and urine urea and creatinine, renal lipid peroxidation along with significant increment (up to P<0.001) in renal enzymatic and non-enzymatic antioxidants. Histological observations of kidney tissues too correlated with the biochemical observations. CONCLUSIONS These finding powerfully supports that S. xanthocarpum fruit extract acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GM both in the biochemical and histopathological parameters and thus validates its ethnomedicinal use.

Chemopreventive effect of Fumaria indica that modulates the oxidant-antioxidant imbalance during N-nitrosodiethylamine and CC14-induced hepatocarcinogenesis in Wistar rats

Abstract Objective To investigation the chemopreventive efficiency of Fumaria indica extract (FIE) on the antioxidant status of N-nitrosodiethylamine (NDEA) and CCl 4 -induced hepatocarcinogenesis in Wistar rats. Methods The experimental animals were divided into six groups ( n = 6). HCC was induced by single intraperitoneal injection of NDEA in normal saline at a dose of 200 mg/kg body weight followed by weekly subcutaneous injections of CCl 4 (3 mL/kg/week) for 6 weeks, as the promoter of carcinogenic effect. After administration of the carcinogen, 200 and 400 mg/kg of FIE were administered orally once a day throughout the study. At the end of 20 weeks, the body weight, liver weight and relative liver weight were measured. The level of hepatic malondialdehyde (MDA) formation, reduced glutathione (GSH) and the activities of antioxidant enzymes viz. CAT, SOD, GPx, and GST in the liver of NDEA and CCL 4 -treated rats were assessed. Results Obtained results demonstrated that the cotreatment with FIE (200 and 400 mg/kg) significantly prevented the decrease of the body weight and also increased in relative liver weight caused by NDEA and CCl4 administration. FIE also significantly prevented hepatic malondialdehyde (MDA) formation and reduced glutathione (GSH) in NDEA-treated rats which were dose dependent. Additionally, FIE also markedly increased the activities of antioxidant enzymes such as CAT, SOD, GPx, and GST in the liver of NDEA and CCL 4 -treated rats. Conclusions These finding powerfully supports that Fumaria indica exert a chemopreventive effect by reversing the oxidant-antioxidant imbalance during hepatocarcinogenesis induced by NDEA and CCl 4 .

Evaluation of chemopreventive effect of Fumaria indica against N-nitrosodiethylamine and CCl4-induced hepatocellular carcinoma in Wistar rats

OBJECTIVE To investigation the chemopreventive potential of Fumaria indica (F. indica) extract (FIE) on N-nitrosodiethylamine and CCl(4)-induced hepatocarcinogenesis in Wistar rats. METHODS The experimental animals were divided into six groups (n=6). Hepatocellular carcinoma was induced by single intraperitoneal injection of N-nitrosodiethylamine (NDEA) in normal saline at a dose of 200 mg/kg body weight followed by weekly subcutaneous injections of CCl(4)(3 mL/kg/week) for 6 weeks, as the promoter of carcinogenic effect. After administration of the carcinogen, 200 and 400 mg/kg of FIE were administered orally once a day throughout the study. At the end of 20 weeks, the body weight, liver weight and relative liver weight were measured. The percentage of nodule incidence and liver cancer markers such as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), γ-glutamyl transferase (γ-GT), total bilirubin level (TBL), α-feto protein (AFP) and carcinoembryonic antigen were estimated along with histopathological investigation in experimental groups of rats. RESULTS Obtained results demonstrated that the cotreatment with FIE significantly prevented the decrease of the body weight and also increased in relative liver weight caused by NDEA. The treatment with FIE significantly reduced the nodule incidence and nodule multiplicity in the rats after NDEA administration. The levels of liver cancer markers such as AST, ALT, ALP, γ-glutamyl transferase, TBL, AFP and carcinoembryonic antigen were substantially increased by NDEA treatment. However, FIE treatment significantly reduced the liver injury and restored the entire liver cancer markers. Histological observations of liver tissues too correlated with the biochemical observations. CONCLUSIONS These finding powerfully supports that F. indica exert chemopreventive effect by suppressing the tumor burden and restoring the activities of hepatic cancer marker enzymes on NDEA and CCl(4)-induced hepatocarcinogenesis in Wistar rats.

Synthesis and Characterization of Cefotaxime Conjugated Gold Nanoparticles and Their Use to Target Drug-Resistant CTX-M-Producing Bacterial Pathogens

Multidrug‐resistance due to “β lactamases having the expanded spectrum” (ESBLs) in members of Enterobacteriaceae is a matter of continued clinical concern. CTX‐M is among the most common ESBLs in Enterobacteriaceae family. In the present study, a nanoformulation of cefotaxime was prepared using gold nanoparticles to combat drug‐resistance in ESBL producing strains. Here, two CTX‐M‐15 positive cefotaxime resistant bacterial strains (i.e., one Escherichia coli and one Klebsiella pneumoniae strain) were used for testing the efficacy of “cefotaxime loaded gold‐nanoparticles.” Bromelain was used for both reduction and capping in the process of synthesis of gold‐nanoparticles. Thereafter, cefotaxime was conjugated onto it with the help of activator 1‐Ethyl‐3‐(3‐dimethylaminopropyl)‐carbodiimide. For characterization of both unconjugated and cefotaxime conjugated gold nanoparticles; UV‐Visible spectroscopy, Scanning, and Transmission type Electron Microscopy methods accompanied with Dynamic Light Scattering were used. We used agar diffusion method plus microbroth‐dilution method for the estimation of the antibacterial‐activity and determination of minimum inhibitory concentration or MIC values, respectively. MIC values of cefotaxime loaded gold nanoparticles against E. coli and K. pneumoniae were obtained as 1.009 and 2.018 mg/L, respectively. These bacterial strains were completely resistant to cefotaxime alone. These results reinforce the utility of conjugating an old unresponsive antibiotic with gold nanoparticles to restore its efficacy against otherwise resistant bacterial pathogens. J. Cell. Biochem. 118: 2802–2808, 2017.

Aerodynamics and deposition effects of inhaled submicron drug aerosol in airway diseases.

Particle engineering is the prime focus to improve pulmonary drug targeting with the splendor of nanomedicines. In recent years, submicron particles have emerged as prettyful candidate for improved fludisation and deposition. For effective deposition, the particle size must be in the range of 0.5-5 μm. Inhalers design for the purpose of efficient delivery of powders to lungs is again a crucial task for pulmonary scientists. A huge number of DPI devices exist in the market, a significant number are awaiting FDA approval, some are under development and a large number have been patented or applied for patent. Even with superior design, the delivery competence is still deprived, mostly due to fluidisation problems which cause poor aerosol generation and deposition. Because of the cohesive nature and poor flow characteristics, they are difficult to redisperse upon aerosolization with breath. These problems are illustrious in aerosol research, much of which is vastly pertinent to pulmonary therapeutics. A technical review is presented here of advances that have been utilized in production of submicron drug particles, their in vitro/in vivo evaluations, aerosol effects and pulmonary fate of inhaled submicron powders.

Silymarin: an insight to its formulation and analytical prospects

Silymarin, a potential phytochemical compound obtained from the seeds of Silybum marianum plant has been used as a hepatoprotective agent for more than a decade. So far, eight active components of silymarin flavonolignans have been identified, among which silibinin has been proven the most active. However, it had poor oral bioavailability due to extensive phase II metabolism, low permeability across intestinal epithelial cells, low aqueous solubility, and rapid excretion in bile and urine. Therefore it becomes necessary to understand all its formulation and analytical aspects from past to present, including all of its possible future prospects. In modern research scenario, nanotization strategies of drugs has served as a potential approach to enhance solubility, bioavailability and to develop a robust formulation. Several approaches have been utilized previously to enhance the solubility and bioavailability of silymarin to provide it a robust strength against physical, chemical, and environmental degradation. Nanoscale formulations such as nanoemulsion, nanosuspension, liposomes, and solid–lipid nanoparticles can be used to enhance solubility and to target them to desired cells with minimum harm to normal cells. However, many other approaches exist such as dendrimers, ceramic nanoparticles, and carbon nanotubes, which serve as a great vehicle in drug delivery to transport medicament at target sites. Therefore, the purpose of this review was to develop a better understanding of the problems associated with silymarin and approaches to overcome the difficulties to develop a better and stable formulation for food and pharmaceutical applications.

Chemopreventive evaluation of Tephrosia purpurea against N-nitrosodiethylamine-induced hepatocarcinogenesis in Wistar rats

Objectives  The chemopreventive potential of Tephrosia purpurea extract (TPE) on N‐nitrosodiethylamine (NDEA)‐induced hepatocellular carcinoma (HCC) in Wistar rats was assessed.

Anti–hepatotoxic potential of Hedyotis corymbosa against D–galactosamine–induced hepatopathy in experimental rodents

Abstract Objective To evaluate hepatoprotective potential of the methanolic extract of Hedyotis corymbosa against D–galactosamine–induced hepatopathy in experimental animals. Methods In the present study, in-vivo hepatoprotective effect of 50% methanolic extract of Hedyotis corymbosa (HCE, 100 and 200 mg/kg body weight) was evaluated using experimental models D–Galactosamine (D–GalN) (200 mg/kg, body weight i.p.) induced hepatotoxicity in experimental animals. The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatise (ALP), γ-glutamyl transferase (γ-GT) and total bilirubin. Meanwhile, in vivo antioxidant activities as lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were screened along with histopathological studies. Results Obtained results demonstrated that the treatment with HCE signi-cantly ( P P P Conclusions The results of this study strongly indicate the protective effect of HCE against acute liver injury which may be attributed to its hepatoprotective activity, and there by scienti-cally support its traditional use.