Toxicopathological effects of feeding aflatoxins B1 in broilers and its ameliosration with indigenous mycotoxin binder.

Mycotoxicosis is the second most important problem faced by the Pakistan poultry industry, after high feed prices. The present experimental study was designed to investigate the toxicopathological effects of aflatoxin B1 (AFB1) in commercial broiler chicks and its amelioration with locally produced mycotoxin binder. Total of 125 broiler chicks was divided into five equal groups (A-E). Group A served as negative control, group B (300 µg AFB1/kg feed) as positive control, group C (300 µg AFB1/kg + Local Mycotoxin Binder (LMB), 1 g/kg feed), group D (300 µg AFB1/kg + 2 g LMB/kg feed), and group E (300 µg AFB1/kg + Commercial Mycotoxin Binder (CMB), 2 g/kg of feed). Parameters studied included mortality, feed intake, bodyweights, absolute and relative organ weights, and gross and microscopic lesions in visceral organs. Clinical signs including alertness, fecal consistency, and feather shine were significantly lower in group B compared with control group A. The feed intake of 2 g/kg LMB treated group was significantly higher than that of the positive control group B. Also mean bodyweights of group D birds was higher than that of group B birds indicating an ameliorative effect of LMB. Histopathological results showed that moldy feed produced necrotic changes in the liver and kidneys in group B birds. However, in group D and E birds, the hepatic and renal parenchyma was normal, showing a protective effect of LMB. In the present study, a higher dose of LMB (2 g/kg) in group D showed higher bodyweights and feed intake. In group D, birds hepatic and renal parenchyma was also normal. The results suggested that local mycotoxin binder ameliorated the toxicopathological effects of AFB1 in mortality, feed intake, bodyweights, organ weights and, gross and microscopic lesions in visceral organs. These ameliorative effects of LMB were dose-dependent. The results of the present study concluded that AFB1 intoxication leads to decrease in bodyweights, feed intake in dose-related manner. The mortality was also dose-dependent. Gross and microscopic changes in the aflatoxin groups were more pronounced, however, all these deleterious effects were ameliorated in higher dose of LMB (group D) and CMB (group E). In group C, these deleterious effects were partially ameliorated. Local mycotoxin binder is an economical solution for aflatoxicosis problem, making poultry production more cost-effective.

Curcuminoid analogs with potent activity against Trypanosoma and Leishmania species.

The natural curcuminoids curcumin (1), demethoxycurcumin (2) and bisdemethoxycurcumin (3) have been chemically modified to give 46 analogs and 8 pairs of 1:1 mixture of curcuminoid analogs and these parent curcuminoids and their analogs were assessed against protozoa of the Trypanosoma and Leishmania species. The parent curcuminoids exhibited low antitrypanosomal activity (EC(50) for our drug-sensitive Trypanosoma brucei brucei line (WT) of compounds 1, 2 and 3 are 2.5, 4.6 and 7.7 microM, respectively). Among 43 curcuminoid analogs and 8 pairs of 1:1 mixture of curcuminoid analogs tested, 8 pure analogs and 5 isomeric mixtures of analogs exhibited high antitrypanosomal activity in submicromolar order of magnitude. Among these highly active analogs, 1,7-bis(4-hydroxy-3-methoxyphenyl)hept-4-en-3-one (40) was the most active compound, with an EC(50) value of 0.053+/-0.007 microM; it was about 2-fold more active than the standard veterinary drug diminazene aceturate (EC(50) 0.12+/-0.01 microM). Using a previously characterized diminazene-resistant T. b. brucei (TbAT1-KO) and a derived multi-drug resistant line (B48), no cross-resistance of curcuminoids was observed to the diamidine and melaminophenyl arsenical drugs that are the current treatments. Indeed, curcuminoids carrying a conjugated keto (enone) motif, including 40, were significantly more active against T. b. brucei B48. This enone motif was found to contribute to particularly high trypanocidal activity against all Trypanosoma species and strains tested. The parent curcuminoids showed low antileishmanial activity (EC(50) values of compounds 1 and 2 for Leishmania mexicana amastigotes are 16+/-3 and 37+/-6 microM, respectively) while the control drug, pentamidine, displayed an EC(50) of 16+/-2 microM. Among the active curcuminoid analogs, four compounds exhibited EC(50) values of less than 5 microM against Leishmania major promastigotes and four against L. mexicana amastigotes. No significant difference in sensitivity to curcuminoids between L. major promastigotes and L. mexicana amastigotes was observed. The parent curcuminoids and most of their analogs were also tested for their toxicity against human embryonic kidney (HEK) cells. All the curcuminoids exhibited lower toxicity to HEK cells than to T. b. brucei bloodstream forms and only one of the tested compounds showed significantly higher activity against HEK cells than curcumin (1). The selectivity index for T. b. brucei ranged from 3-fold to 1500-fold. The selectivity index for the most active analog, the enone 40, was 453-fold.