The effect of griseofulvin treatment on signal grass (Brachlaria decumbens) toxicity was studied in 27 male Wiltshire Indigenous Malaysian crossbred sheep. Grazing on signal grass generally decreased the activity of the drug metabolizing enzymes in livers and kidneys. Griseofulvin oral administration of 5 mg/kg body weight for 5 consecutive days every other week for 10 w increased the hepatic concentration of cytochrome P-450 and the activity of phase II drug metabolizing enzymes (UDP-glucuronyltransferase and glutathione-S-transferase) while it decreased the hepatic and increased the renal activity of phase I enzymes aminopyrine-N-demethylase and aniline-4-hydroxylase. Griseofulvin did not protect sheep against B decumbens toxicity as 5/7 animals treated with griseofulvin and grazed on B decumbens showed signs of the plant toxicity.
Samples of Brachiaria decumbens collected from 5 farms representing the Peninsular Malaysia were subjected to selected trace mineral and phytate analyses to explain the pathogenesis of B decumbens intoxication. Concentrations of Cu, Zn, Fe and Mo were comparable to other grasses while that of phytate was low. The molar ratios of Cu:Zn, Cu:Mo, and Cu:Fe warrant that Cu deficiency is involved in the toxicity of B decumbens. This might aggravate the development of photosensitization of unpigmented or lightly pigmented areas of affected animals. The Zn:phytate ratio could predispose to Zn deficiency during intoxication.
The influence of copper (Cu) overload on hepatic lipid peroxidation and antioxidation defense capacity was studied by overloading rats with copper sulphate orally (500 mg Cu/kg bw) 5 d/w for 8 w. Malondialdehyde (MDA), Cu-Zn superoxide dismutase (SOD), and Se-glutathione peroxidase (GSH-Px) were measured in serum and liver homogenate at 2, 4 and 8 w of dosing. Liver Cu concentration and alanine aminotransferase (ALT) activity were also determined. As Cu loading progressed, there were multiparameter changes with significant ALT elevation, increased MDA concentrations in serum and liver homogenate, and dramatic declines of SOD and GSH-Px activities in erythrocytes and whole blood respectively, along with marked elevation of hepatic Cu in the Cu-dosed group. Excessive Cu accumulation in the liver depressed SOD and GSH-Px activities and resulted in high MDA in serum and liver homogenate due to the lipid peroxidation induced by the Cu overload.
The effect of Brachiaria decumbens (signal grass) on drug-metabolizing enzymes was studied in sheep. After 14 d of grazing a pure signal grass pasture, significant declines were observed in hepatic aminopyrine N-demethylase and aniline 4-hydroxylase (phase I biotransformation) and in conjugative enzymes UDP-glucuronyltransferase and glutathione S-transferase. Kidney enzymes were significantly decreased except for UDP-glucuronyltransferase. Enzyme activities were also compared for normal sheep and cattle livers and kidneys. Lower activities were found in cattle, indicating that factors other than biotransformation are responsible for the clincial tolerance of cattle to B. decumbens toxicity.
An attempt was made to clarify the association between zinc (Zn) and antioxidants due to Zn supplementation on lipid peroxidation occurring during Brachiaria decumbens intoxication. The concentration of Zn, copper, malondialdehyde (MDA), superoxide dismutase (SOD), and gluthathione peroxidase (GSH-Px) were determined in tissues. There was a gradual increment in the concentration of Zn and MDA in serum and hepatocytic SOD in groups given Zn + B decumbens. A decline in erythrocytic GSH-Px and SOD, and lower concentration of reduced glutathione in hepatocyte cytosols were also detected in these sheep. It is highly suggestive that Zn supplementation may depress antioxidant status and enhance lipid peroxidation during B decumbens intoxication.
The toxicities of ROUNDUP and its component chemicals, glyphosate (N-phosphonomethylglycine) and polyoxyethyleneamine (POEA), were determined at 0, 1, 3, 6 and 24 h following administration to rats. The intratracheal administration of glyphosate (0.2 g/kg), POEA (0.1 g/kg), a mixture of glyphosate (0.2 g/kg) + POEA (0.1 g/kg), or ROUNDUP (containing 0.2 g/kg glyphosate and 0.1 g/kg POEA) elicited immediate respiratory effects which were more severe and which lasted longer in the groups receiving the POEA-containing preparations than in the glyphosate alone group. By 1 h, all test preparations had caused deaths, but more occurred from the POEA-containing preparations than from glyphosate. The po administration of POEA (1 g/kg), the mixture of glyphosate (2 g/kg) +POEA (1 g/kg), or ROUNDUP (containing 2 g/kg glyphosate and 1 g/kg POEA) produced diarrhea and blood-stained weeping from noses. Death was only seen from POEA at 24 h. Glyphosate (2 g/kg po) produced transient diarrhea without nose bleeds; POEA caused diarrhea at 1 h; and the mixture of POEA + glyphosate produced diarrhea later that increased in severity with time. Bloody nose secretions were seen only with the preparations that contained POEA. No deaths, respiratory effects or bloody nose secretions occurred in controls given saline. Both POEA and glyphosate caused lung hemorrhages and lung epithelial cell damage with po or intratracheal exposures. These results indicate POEA and preparations that contained POEA were more toxic than glyphosate.
Spectroscopic examinations of purified extracts of the rumen content of sheep intoxicated by Brachiaria decumbens revealed the presence of a mixture of sapogenins, identified as 3-spirostanols. These isomeric steroid sapogenins (C27H44O3) are believed the toxic principles in causing toxicity in sheep after feeding on B. decumbens.
Brachiaria decumbens toxicity resulted in an altered reticulorumen environment in the sheep. This adversely affected the growth and activity of microorganisms in the rumen as reflected by greatly decreased concentrations of the volatile fatty acids (acetic, propionic and butyric) in B decumbens-intoxicated sheep.
Severe neurological dysfunction was observed in sheep 4 weeks after grazing on Signal grass (Brachiaria decumbens). These neurological disorders included the stamping of forelegs, star-gazing, incoordination, head-pressing against the fence and circling movements. Histologically, numerous vacuolations of various sizes were observed in the white matter of the brain giving rise to a spongy appearance.
In addition to generalized icterus, enlargement of the liver and severe photosensitization, signal grass (Brachiaria decumbens) toxicity also caused ruminal stasis and a decreased rumen pH in sheep. Ruminal stasis, which occurred within 3 weeks of grazing on this grass, may be the effect of the toxin produced in the rumen rather than a sequele of a decreased rumen pH. Animals were anorexic and the volume of their rumen content was very much reduced.