Expression of nutrient transporter genes in response to dietary rice gluten meal and protease enzyme supplementation and the consequent effects on growth, nutrient digestibility, immunity and jejunum histomorphometry in chicken.

The objective of this study was to investigate the effects of feeding rice gluten meal (RGM) as an alternative protein source along with protease enzyme supplementation on growth performance, expression of nutrient transporter genes, nutrient digestibility, immune response and gut histomorphometry of broiler chicken. Proximate analysis of RGM revealed 923 g dry matter (DM), 500 g crude protein (CP), 69.2 g ether extract, 94.7 g crude fiber, 215.4 g nitrogen-free extract, 43.7 g ash, 6.20 g calcium, 7.80 g total phosphorus, 18.99 MJ gross energy and 12.68 MJ metabolizable energy per kg diet. Significant upregulation of nutrient transporter genes (PepT1, EAAT3 and mucin) and better growth performance was observed in the birds fed control diet which was statistically similar to the birds fed 150 g RGM compared to birds fed higher RGM levels. Histomorphometry of jejunum, nutrient digestibility, and immune response of birds did not reveal any significant effect of RGM or protease enzyme supplementation. However, the inclusion of RGM up to 150 g/kg diet resulted in significant decline of feed cost/kg live weight gain, dressed meat yield and eviscerated meat yield by 13.13%, 12.99% and 13.36%, respectively compared to control. Thus, it was concluded that the inclusion of 150 g RGM/kg diet in broiler chicken ration has no adverse effects on the growth pattern of birds and can be used for least-cost feed formulation for chicken.

Hepatic transcriptome analysis reveals altered lipid metabolism and consequent health indices in chicken supplemented with dietary Bifidobacterium bifidum and mannan-oligosaccharides.

This study investigated the role of dietary prebiotic mannan-oligosaccharides (MOS), and probiotic Bifidobacterium bifidum (BFD) in lipid metabolism, deposition, and consequent health indices in broiler chicken. The supplementation of 0.2% MOS along with either 106 or 107 CFU BFD/g feed resulted in downregulation of Acetyl-CoA carboxylase, fatty acid synthase, sterolregulatory element binding protein-1, and apolipoprotein B100; and up-regulation of peroxisome proliferator activated receptor-α AMP-activated protein kinase α-1, and stearoyl CoA (∆9) desaturase-1 hepatic expression in broiler chicken. The birds supplemented with 0.2% MOS along with either 106 or 107 CFU BFD/g feed depicted lower body fat percentage, palmitic acid, stearic acid, and saturated fatty acid contents, whereas, higher palmitoleic acid, oleic acid, and MUFA contents were observed. The ∆9-desaturase indices of chicken meat have shown higher values; and elongase index (only thigh) and thioesterase index have shown lower values in birds supplemented with 0.2% MOS along with either 106 or 107 CFU BFD/g feed. The meat health indices such as Polyunsaturated fatty acids (PUFA)/Saturated fatty acids (SFA) ratio, Mono-saturated fatty acids (MUFA)/SFA ratio, unsaturated fatty acids (UFA)/SFA ratio, hypocholesterolemic/hypercholesterolemic fatty acid ratio, saturation index, atherogenic index, thrombogenic index, and hypercholesterolemic fatty acid content were positively improved in birds supplemented with 0.2% MOS along with either 106 or 107 CFU BFD/g feed. Similarly, the birds supplemented with 0.2% MOS along with either 106 or 107 CFU BFD/g feed have shown lower serum triglyceride and total cholesterol levels along with higher high density levels and improved serum health indices cardiac risk ratio, atherogenic coefficient, and, atherogenic index of plasma.

A comparative study on the antioxidant status, meat quality, and mineral deposition in broiler chicken fed dietary nano zinc viz-a-viz inorganic zinc.

Use of nano minerals in farm animal nutrition offers considerable advantages over inorganic or organic mineral sources. But, the conventional chemical synthesis of nano minerals suffers from disadvantage of possible environmental accumulation and pollution due to the non-biodegradable materials and chemicals. This study investigated the effects of green nano-zinc (GNZ) and market nano-zinc (MNZ) with respect to the inorganic zinc (IZ) on meat quality, antioxidant status, mineral deposition, and bone development in broiler chicken. Following a 3 × 3 factorial design, nine dietary treatments were formulated by employing three levels (40, 60, and 80 ppm) and three sources (inorganic, green nano, and market nano) of zinc viz. IZ-40, GNZ-40, MNZ-40, IZ-60, GNZ-60, MNZ-60, IZ-80, GNZ-80, MNZ-80. Six replicates of broiler chicken were assigned to each treatment with eight birds in each. The birds fed 80 ppm Zinc of either GNZ or MNZ source resulted in significantly higher serum SOD, glutathione peroxidase, catalase, zinc, calcium, and phosphorus levels; increased bone dimensions, weight, total ash, phosphorus, and zinc content along with higher liver and muscle zinc concentration. The meat of chicken fed 80 ppm zinc of MNZ source followed by GNZ source has shown significantly better antioxidant (DPPH and ABTS values) status and lower lipid peroxidation (free fatty acid and TBARS values). The 80 ppm zinc of either MNZ or GNZ source resulted in significantly lower fat and cholesterol content of chicken meat compared to lower Zn levels and IZ source. This study indicated that 80 ppm dietary zinc of either MNZ or GNZ source improved the antioxidant status, and reduced the meat cholesterol, fat content, and lipid peroxidation of chicken meat along with increased bone dimensions and mineralization.

Dietary Lactobacillus acidophilus and Mannan-Oligosaccharides Alter the Lipid Metabolism and Health Indices in Broiler Chickens.

The effects of dietary Lactobacillus acidophilus (LBA) and mannan-oligosaccharide (MOS) supplementation on lipid metabolism and consequent lipid profile and health indices in broiler chicken were investigated in this study. Supplementation of 0.2% MOS along with either 106 or 107 LBA/g feed in broiler chicken downregulated hepatic expression of genes involved in lipogenesis, and upregulated expression of lipolytic genes. It caused decline of lipogenesis and increase of lipid oxidation which resulted in lower carcass fat content. None of the genes studied influenced fatty acid profile of chicken meat except the expression of stearoyl CoA (Δ9) desaturase-1 (SCD-1) whose upregulation increased monounsaturated fatty acid (MUFA) content at the cost of saturated fatty acid (SFA) content. The lipid metabolism indices of chicken meat such as ∆9 desaturase index (DI) increased in birds supplemented with 0.2% MOS along with either 106 or 107 CFU LBA/g feed, whereas no effect was observed on ∆5 + ∆6 DI. The supplementation of 0.2% MOS along with either 106 or 107 CFU LBA/g feed in birds improved the health indices of chicken meat due to upregulation of SCD-1 expression. The supplementation of 0.2% MOS along with either 106 or 107 CFU LBA/g feed in broiler chicken produced hypocholesterolemic and hypolipidemic effects with improved serum cardio-protective indices.

Challenges and prospects of COVID-19 vaccine development based on the progress made in SARS and MERS vaccine development.

The outbreak of coronavirus disease 2019 (COVID-19) as a pandemic has shaken the global health system and economy by their roots. This epidemic is still spreading and showing no signs of decreasing trend. Vaccination could be the only effective and economical means to control this pandemic. A number of research institutions and pharmaceutical companies have plunged into the race of vaccine development against COVID-19 which are in various stages of development. An intriguing fact of coronavirus infections is that in every decade of the 21st century there is a new major coronavirus epidemic, namely, severe acute respiratory syndrome (SARS) in 2002, Middle East respiratory syndrome (MERS) in 2012, and now COVID-19; and such epidemics are expected in future too. Since most of the biological characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are still obscure, the scientists are relying on the information available on SARS-CoV and to some extent on MERS-CoV for designing and developing COVID-19 vaccines. But there is a need of vigorous testing for immunogenicity, safety, efficacy, and level of protection conferred in the hosts. This review focuses on the challenges and prospects of vaccine development against COVID-19. It highlights seriousness, bottlenecks in vaccine development, possible vaccine candidates, different vaccine strategies, safety evaluation issues, and vaccine production processes pertaining to COVID-19 based on the knowledge acquired on SARS and MERS vaccine development in the past.

Prevalence of dermatophytosis in animals and antifungal susceptibility testing of isolated Trichophyton and Microsporum species.

Dermatophytosis is a frequently encountered dermatological problem in domestic and pet animals which negatively affects animal health and production. This study investigated the prevalence of dermatophytosis in different animals and carried antifungal susceptibility testing in the northern Indian state of Uttarakhand. A total of 157 clinical samples were collected from the animals irrespective of sex and age during a time period of 3 years from December 2016 to December 2019. Direct microscopy, fungal culture, isolation, identification, and antifungal susceptibility testing were carried out. Direct microscopy and in vitro culture were equally efficient in diagnosis of dermatophytosis. The prevalence of dermatophytes ranged between 45 and 53.3% and Trichophyton mentagrophytes was the most abundant species (38%) followed by Microsporum canis (21.5%). All the species observed were isolated from goats and dogs except T. tonsurans and M. nanum, respectively. All the isolated dermatophytes were urease test positive except T. rubrum and T. verrucosum. The hair perforation test was negative for M. audouinii, along with T. rubrum and T. verrucosum, whereas only M. canis was positive for rice grain test. Only T. mentagrophytes, T. rubrum, T. verrucosum, and T. tonsurans were able to show optimum growth at 37 °C. Maximum inhibition of fungal growth was exhibited by clotrimazole and least by fluconazole.

Dietary synbiotic supplementation improves the growth performance, body antioxidant pool, serum biochemistry, meat quality, and lipid oxidative stability in broiler chickens.

The present study investigated the effects of Lactobacillus acidophilus (LBA) and mannan-oligosaccharides (MOS) supplementation on the production performance, serum biochemistry, antioxidant profile, health indices, meat quality, and lipid oxidative stability of broiler chicken. A total of 252 commercial broiler chickens at 1 d old of uniform body weight were randomly allocated to 6 maize-soybean-based dietary treatments: T1 (control diet), T2 ( antibiotic bacitracin methylene di-salicylate [BMD] at 20 mg/kg diet), T3 (MOS at 0.1% + LBA at 106 CFU/g feed), T4 (MOS at 0.1% + LBA at 107 CFU/g feed), T5 (MOS at 0.2% + LBA at 106 CFU/g feed), and T6 (MOS at 0.2% + LBA at 107 CFU/g feed). Each treatment was assigned to 6 replicates of 7 birds. The samples for meat quality and serum biochemistry analysis were taken from 12 birds per treatment (2 birds/replicate). The results revealed better (P < 0.01) growth performance and production efficiency of birds fed either T5 or T6 diet compared to control or BMD supplemented diet and BMD-supplemented birds superseded the control birds. Higher (P < 0.01) serum and liver antioxidant enzyme activities, meat antioxidant capacity (2, 2-azinobis-3-ethylbenzothiazoline-6-sulfonic acid [ABTS] and 1, 1-diphenyl-2-picrylhydrazyl [DPPH] assays], serum total protein, high-density lipoproteins (HDL) cholesterol (P < 0.05), and globulin levels (P < 0.01) were observed in birds fed either T5 or T6 diet compared to control or BMD supplemented birds, whereas, lower lipid oxidation (P < 0.01), cardiac risk ratio, atherogenic coefficient, atherogenic index of plasma, serum glucose, triglyceride, total cholesterol levels (P < 0.01), and serum albumin-to-globulin ratio (P < 0.05) were observed in the chickens. The pH of meat from birds fed T4, T5 or T6 diet was lower (P < 0.01) compared to control and other treatments. The extract release volume (ERV), water holding capacity (WHC), and protein content of meat were higher (P < 0.05) in birds fed either T5 or T6 diet compared to control or BMD supplemented birds. Thus, it was concluded that the supplementation of 0.2% MOS along with LBA at 106 CFU/g is optimum for better growth performance, serum biochemistry, antioxidant profile, health indices, meat quality, and lipid oxidative stability of broiler chickens.

Dietary Mannan-oligosaccharides potentiate the beneficial effects of Bifidobacterium bifidum in broiler chicken.

This study investigated the effects of dietary Bifidobacterium bifidum (BFD) and mannan-oligosaccharide (MOS), as a synbiotic, on the production performance, gut microbiology, serum biochemistry, antioxidant profile and health indices of broiler chicken. Six dietary treatments were T1 (negative control), T2 (positive control-20 mg antibiotic BMD kg-1 diet; BMD: bacitracin methylene disalicylate), T3 (0·1% MOS + 106  CFU BFD per g feed), T4 (0·1% MOS + 107  CFU BFD per g feed), T5 (0·2% MOS + 106  CFU BFD per g feed) and T6 (0·2% MOS + 107  CFU BFD per g feed). Significantly (P < 0·01) better growth performance and efficiency was observed in birds supplemented with 0·2% MOS along with 106  CFU BFD per g of feed compared to BMD and control birds. Supplementation with 0·2% MOS along with either 106 or 107  CFU BFD per g feed reduced (P < 0·01) the gut coliform, Escherichia coli, total plate count, and Clostridium perfringens count and increased the Lactobacillus and Bifidobacterium count. Significantly (P < 0·01) higher serum and liver antioxidant enzyme pool, serum HDL cholesterol and lower serum glucose, triglyceride, total cholesterol, cardiac risk ratio, atherogenic coefficient and atherogenic index of plasma were observed in birds supplemented with 0·2% MOS along with 106  CFU BFD per g of feed compared to control or BMD supplemented birds. Better production performance, gut microbial composition, serum biochemistry, antioxidant profile and health indices were depicted by broiler chicken supplemented with 0·2% MOS and 106  CFU BFD per g of feed.

Comparative study on the responses of broiler chicken to hot and humid environment supplemented with different dietary levels and sources of selenium.

Present study was carried out with the objective of investigating the role of green synthesized nano Se (GNS) in growth performance, digestibility of minerals, immunity, stress alleviation, antioxidant status, and body Se content of broiler chicken raised under hot and humid environment with respect to market nano Se (MNS) and inorganic Se. The experimental design was 3 × 3 factorial, in which three levels (0.15, 0.20, and 0.25 ppm) and three sources (inorganic, green nano, and market nano) of Se resulted in nine treatments viz. IS-0.15, GNS-0.15, MNS-0.15, IZ-0.20, GNS-0.20, MNS-0.20, IS-0.25, GNS-0.25, and MNS-0.25 (IS: inorganic Se, GNS: green nano Se, MNS: market nano Se). A total of 432 broiler chicken were divided among nine treatments with six replicates of birds per treatment (8 birds/replicate). Results of present study revealed significantly better growth performance of birds supplemented with 0.25 ppm nano Se. The supplementation of 0.25 ppm nano Se improved the immune response and lymphoid organ development of birds. Significantly higher Se and nitrogen digestibility coefficients, serum antioxidant activity and decline of Heterophil: Lymphocyte ratio and expression of HSP70 gene were observed in birds supplemented with 0.25 ppm Se and nano source of Se compared to inorganic Se. Significantly higher Se concentration in liver and breast muscle and higher serum Se concentration were observed in birds fed 0.25 ppm nano Se. The liver Se concentration was much higher than that of breast muscle. However, the nano Se synthesized by green method in this study did not differ significantly from the chemically synthesized nano Se. It was concluded that 0.25 ppm Se and nano form of Se are superior to lower levels and inorganic form of Se, respectively, in improving the immunity, growth, antioxidant status, and in stress alleviation of broiler chicken. However, GNS is equally efficient as chemically synthesized MNS.

Recent advances in the diagnosis of dermatophytosis.

Dermatophytosis is a disease of global significance caused by pathogenic keratinolytic fungi called dermatophytes in both animals and humans. The recent taxonomy of dermatophytes classifies them into six pathogenic genera, namely Microsporum, Trichophyton, Epidermophyton, Nannizzia, Lophophyton and Arthroderma. It is because of the delayed diagnostic nature and low accuracy of dermatophyte detection by conventional methods that paved the path for the evolution of molecular diagnostic techniques, which provide the accurate and rapid diagnosis of dermatophytosis for an appropriate, timely antifungal therapy that prevents the nonspecific over-the-counter self-medication. This review focuses on the importance of rapid and accurate diagnosis of dermatophytosis, limitations of conventional methods, selection of targets in diagnosis, and factors affecting sensitivity and specificity of various molecular diagnostic technologies in the diagnosis of dermatophytosis. Generally, all the molecular techniques have a significant edge over the conventional methods of culture and microscopy in the dermatophytosis diagnosis. However, in mycology laboratory, the suitability of any molecular diagnostic technique in the diagnosis of dermatophytosis is driven by the requirement of time, economy, complexity, the range of species spectrum detected and the scale of diagnostic output required. Thus, various choices involved in the pursuit of a diagnosis of dermatophytosis are determined by the available conditions and the facilities in the laboratory.

Dietary flaxseed and turmeric is a novel strategy to enrich chicken meat with long chain ω-3 polyunsaturated fatty acids with better oxidative stability and functional properties.

The purpose of the present study was to elucidate the effects of feeding flaxseed meal (FSM) and turmeric rhizome powder (TRP) supplementation on tissue lipid profile, lipid metabolism, health indices, oxidative stability, and physical properties of broiler chicken meat. The 100 g FSM along with 10.0 g TRP supplementation significantly increased the ω-3 PUFA, particularly ALA, EPA, DPA, and DHA of broiler chicken meat due to the corresponding increase ∆9 and Δ5 + Δ6 desaturase activities. The increased activities of the desaturases resulted in significantly better health indices of the broiler chicken meat. The feeding of 100 g FSM along with 10.0 g TRP supplementation reduced the atherogenic and thrombogenic indices of broiler chicken meat. The 100 g FSM feeding reduced the oxidative stability, water holding capacity, extract release volume of broiler chicken meat and increased drip loss, whereas, 10.0 g TRP supplementation reversed these negative effects of FSM.

Dynamics of gene expression of hormones involved in the growth of broiler chickens in response to the dietary protein and energy changes.

The synergy between the genetic potential and the nutrient intake determines the growth performance of meat-type chicken and nutrigenomics approach helps us understand the response of candidate genes of growth in chicken to dietary manipulations. The current study aimed to assess the growth performance and expression of hepatic growth related genes in the naked neck broiler chicken in response to different dietary energy and protein levels with a hypothesis that high plane of nutrition enhances both of these positively. The results revealed that birds have shown significantly better growth performance under high protein (HP) and high energy (HE) dietary regime. The expression profiles of the genes studied revealed upregulation of IGF-1, IGF-2, and GH under dietary HP and HE regime relative to other protein and energy levels with greater upregulation at 3rd week than the 1st and 5th week of age of birds. The IGFR and GHR mRNA expression was significantly higher under HP and HE dietary regimen with an increasing and decreasing trend from 1st to 5th week of age, respectively. A consistent and significant downregulation of IGFBP-2 was observed under HP and HE regime throughout the feeding trial. The myostatin expression was higher at 3rd week of age followed by 1st week expression. The HP and HE as well as LP (Low protein) and HE diet resulted in significant upregulation of myostatin gene expression in liver. In support to the set hypothesis of this study the high protein and high energy diet resulted in better growth performance of broiler chickens with corresponding upregulation of IGF-1, IGF-2, IGFR, GH, GHR, and Myostatin gene expression and downregulation of IGFBP-2 in liver.

Feeding value of rice distiller's dried grains with solubles as protein supplement in diet of laying hens.

A feeding trial of 10 weeks duration was undertaken on laying hens (n = 240) to evaluate feeding value of rice distiller's dried grains with soluble (rDDGS) with or without enzyme supplementation (α-amylase, ß-glucanase, xylanase, carboxymethylcellulase, pectinase, proteinase, α-galactosidase, ß-galactosidase, lipase, and phytase), following 4 × 2 factorial design, on egg production, nutrient utilization, and cost economics of egg production. The birds were randomly assigned to eight dietary treatments with 30 birds/treatment. The birds were housed individually in layer cages and each bird was taken as an experimental unit. Eight experimental diets were prepared by incorporating four levels (0, 50, 75, and 100 g/kg) of rDDGS with and without enzyme supplementation. The results revealed a significant (P < 0.01) increase of egg mass, feed intake, egg production, and body weight gain in dietary treatments with up to 75 g rDDGS though the values were statistically similar to the hens fed 100 g rDDGS. Enzyme supplementation resulted in significant (P < 0.01) improvement of egg mass, egg production, feed conversion ratio (FCR) per dozen eggs, FCR per kilogramme egg mass, and net FCR. The significantly (P < 0.01) higher yolk index was observed at 100 g rDDGS level, while shell thickness improved significantly (P < 0.01) up to 75 g rDDGS level. No significant effect of rDDGS inclusion was observed on shape index, albumin index, and Haugh unit. Enzyme supplementation significantly improved the shell thickness and yolk colour of eggs. Nitrogen, calcium, and phosphorus retention and dry matter metabolizability did not show any significant treatment effects. There was significant (P < 0.01) reduction in feed-cost per kilogramme egg mass or per dozen eggs with the increased DDGS levels and dietary enzyme supplementation. It was concluded that rDDGS can be used up to 100 g/kg diet of laying hens along with enzyme supplementation for better productivity of layer hens.

Effect of dietary saponin rich soapnut (Sapindus mukorossi) shell powder on growth performance, immunity, serum biochemistry and gut health of broiler chickens.

This study was conducted to evaluate the effects of dietary soapnut (Sapindus mukorossi) shell powder (SSP), a cheap source of saponins, on growth performance, immunity, serum biochemistry and gut health of broiler chickens. The experimental design was 4×2, employing four saponin levels (0, 100, 150 and 200 mg/kg diet), each provided for two time durations (0-42 day and 21-42 day) resulting into eight dietary treatments. Results revealed no significant effect of dietary saponins on body weight gain, feed intake and feed conversion ratio of birds. The abdominal fat percentage, heterophil to lymphocyte ratio, serum cholesterol and triglyceride levels, faecal total plate count, coliform count and E. coli count decreased (p < .05) progressively with increasing saponin levels and lower values were observed at 150 mg and 200 mg saponin levels. Significant improvement of cell-mediated and humoral immune response was observed in birds fed 150 mg and 200 mg saponin compared to control. The serum glucose concentration was significantly (p < .05) higher in control group compared to other groups. No significant effects of dietary saponin were observed on carcass characteristics, faecal Lactobacillus count, intestinal histomorphometry and cost economics of broiler chicken production. Thus, dietary saponins at 150 mg/kg diet as SSP for three weeks (21-42 days) was optimum for better immunity and welfare of birds without adverse effects on the growth performance.

Ameliorative effect of ursolic acid on renal fibrosis in adenine-induced chronic kidney disease in rats.

Ursolic acid (UA), an ursane-type pentacyclic triterpenoid commonly found in apple peels and holy basil has been shown to possess many beneficial effects. Renal fibrosis is a complication of kidney injury and associated with increased risk of morbidity and mortality. In our previous investigation, a lupane-type pentacyclic triterpenoid, betulinic acid (BA) was found to have protective effect on chronic kidney disease (CKD) and renal fibrosis. This prompted us to explore the therapeutic value of UA, a chemically related compound to BA in CKD. CKD was induced by feeding adenine with the feed at a concentration of 0.75% for 28 days. UA at the dose rate of 30 mg/kg in 0.5% carboxy methyl cellulose (CMC) was administered by oral route, simultaneously with adenine feeding for 28 days. Adenine feeding increased the kidney weight to body weight index, decreased the kidney function due to injury as indicated by increased markers like serum urea, uric acid, creatinine, cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) and initiated the fibrotic response in kidney by increasing the profibrotic proteins viz. transforming growth factor-beta (TGF-ß), connective tissue growth factor (CTGF), fibronectin and collagen. However, treatment with UA reversed the damage induced by adenine as shown by reduced kidney injury and fibrosis markers which was further clearly evident in histological picture indicating the suitability of UA for use in CKD.

Betulinic acid attenuates renal oxidative stress and inflammation in experimental model of murine polymicrobial sepsis.

Sepsis is a common cause of acute kidney injury (AKI) and is associated with substantial morbidity and mortality. Objective of the study was to evaluate the effect of betulinic acid, a triterpenoid in sepsis-induced AKI using cecal ligation puncture (CLP) mouse model. Mice subjected to CLP developed histologic AKI at 18h after CLP. There was an increase in renal proinflammatory response (nuclear factor-kappa B expression, tumor necrosis factor-alpha, interleukin (IL)-6 and IL-10), matrix metalloproteinase-9, plasma creatinine, renal neutrophil gelatinase-associated lipocalin and oxidant stress response (malondialdehyde, inducible nitric oxide synthase, total nitrite and superoxide); decrease in anti-oxidant levels (superoxide dismutase and catalase) at 18h of CLP. However, BA pretreatment at the doses of 10 and 30mg/kg prevented the CLP-induced kidney damage by restoring the aforementioned inflammatory mediators, oxidant and anti-oxidant imbalance. These evidences suggest that, the protective effects of BA on kidney are associated with defending action against inflammatory and oxidative stress response in CLP mice and BA could be potential therapeutic agent in sepsis-induced AKI.

Betulinic acid attenuates lung injury by modulation of inflammatory cytokine response in experimentally-induced polymicrobial sepsis in mice.

Sepsis commonly progresses to acute lung injury (ALI), an inflammatory lung disease with high morbidity and mortality. Septic ALI is characterized by excessive production of proinflammatory mediators. It remained refractory to present therapies and new therapies need to be developed to improve further clinical outcomes. Betulinic acid (BA), a pentacyclic lupane group triterpenoid has been shown to have anti-inflammatory activities in many studies. However, its therapeutic efficacy in polymicrobial septic ALI is yet unknown. Therefore, we investigated the effects of BA on septic ALI using cecal ligation and puncture (CLP) model in mice. Vehicle or BA (3, 10, and 30mg/kg) was administered intraperitoneally, 3 times (0, 24 and 48h) before CLP and CLP was done on 49(th)h of the study. Survival rate was observed till 120h post CLP. Lung tissues were collected for analysis by sacrificing mice 18h post CLP. BA at 10 and 30mg/kg dose significantly reduced sepsis-induced mortality and lung injury as implied by attenuated lung histopathological changes, decreased protein and neutrophils infiltration. BA also decreased lung NF-κB expression, cytokine, intercellular adhesion molecule-1, monocyte chemoattractant protein-1 and matrix metalloproteinase-9 levels. These evidences suggest that, the protective effects of BA on lungs are associated with defending action against inflammatory response and BA could be a potential modulatory agent of inflammation in sepsis-induced ALI.

Betulinic acid negates oxidative lung injury in surgical sepsis model.

BACKGROUND: Sepsis commonly progresses to acute lung injury and is associated with high morbidity and mortality. Septic acute lung injury is characterized by severe oxidative stress response, remained refractory to present therapies, and new therapies need to be developed to improve further clinical outcomes. We determined the effect of betulinic acid (BA) on oxidative lung injury in mice using cecal ligation and puncture (CLP) model. MATERIALS AND METHODS: Five groups of mice (six in each group) received three pretreatments at 24-h interval before surgery. Surgery was done 1 h after last dosing. Sham and CLP control group mice received vehicle. BA was administered to other three groups of mice at 3, 10, and 30 mg/kg dose. Lung and plasma samples were collected for analysis by sacrificing the mice at 18 h of surgery. RESULTS: Compared with sham, CLP significantly increased total protein, nitrite, malondialdehyde, isoprostane, superoxide, protein carbonyl, oxidative stress index, inducible nitric oxide synthase protein, and histopathologic changes and reduced the superoxide dismutase, catalase activity, and total thiol levels in lungs and plasma, which were restored by BA pretreatment. CONCLUSIONS: BA pretreatment decreased the levels of oxidants, increased the levels of antioxidants in lungs and plasma thereby reducing the oxidative lung injury in CLP mice. Additionally, BA was found to scavenge the superoxide and nitric oxide radical in vitro. Thus, BA is suggested to be effective in treatment of oxidative lung injury in sepsis.