Approximately 600 species of Crotalaria (family Fabaceae; rattle pods) grow in tropical and subtropical regions of the world. Several species of Crotalaria are sources of the hepatotoxic pyrrolizidine alkaloid (PA) monocrotaline, which sporadically poisons grazing horses, cattle, sheep, and pigs, as well as poultry whose feed grain is contaminated with their seeds.[3-6] The acute poisoning and death of cattle occur because of a large intake of Crotalaria over a short period under conditions of natural grazing. Acute poisoning is characterized by extensive damage, necrosis, and hemorrhage of the liver,[7, 8] which is the only abnormality recorded. PAs are monoesters and diesters of the pyrrolizidine necine bases retonecine and otonecine from a variety of plant species, with 1,2-unsaturation of the necine base required for hepatoxicity.[9-11] New reports on PA plant toxicity continue to be recorded from various parts of the world in the veterinary and other scientific literature. Nonetheless, Crotalaria poisoning is underreported. Various diet supplement treatments are ineffective against PA intoxication in livestock.[12-15] Poisoned animals with clinical signs rarely recover; therefore, prevention is the best control measure. Veterinary teams usually use local remedies for Crotalaria poisoning, for example, peanut oil, atropine sulfate, and antidiarrheal agents.
Sesame oil, from the seeds of Sesamum indicum, protects against multiple organ failure, sepsis, hepatic injury after cecal ligation and puncture, endotoxemic renal injury, septic hepatic injury, and acetaminophen-induced acute hepatic damage. Sesame oil as a dietary supplement and nutraceutical alleviates many types of diseases in rodent models.[22-24] Sesame oil contains sesamin, sesamol, and sesamolin, all of which contribute to its antioxidant property. Sesame oil offers better protection than other dietary oils, such as peanut oil, against hypertension, hyperlipidemia, and lipid peroxidation by modulating in vivo antioxidants. Furthermore, sesamol, an active ingredient of sesame oil, therapeutically attenuates monocrotaline-induced acute liver damage. Therefore, monocrotaline poisoning in rats is used as a model for similar poisoning in cattle. We hypothesized that sesame oil would prevent acute monocrotaline poisoning in rats. In this study, we compared the therapeutic effects of sesame oil and peanut oil on acute monocrotaline poisoning in rats.
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We found that early pancreatic and lung injury and then late liver injury contributed to acute monocrotaline poisoning in rats. Acute ovine intoxication from a single dose of Crotalaria retusa seeds (205.2 mg of monocrotaline/kg body weight) caused mild jaundice and the death of sheep within 12 hours.[29, 33] Necropsy and histology of the liver disclosed a nutmeg appearance, centrilobular necrosis, and hepatic periacinar necrosis.[29, 33] We treated all the rats with the same dose of monocrotaline, and the rats were all able to survive to 24-hour post poisoning with no mortality during this experiment. However, we found that serum amylase activity had decreased and that severe pancreatic and lung injury had developed within 6 hours, but that serum AST and ALT activity and hepatic injury had peaked 24 hours after acute monocrotaline poisoning. Therefore, we hypothesize that the death of the sheep in Anjos et al and Nobre et al may have been because of early pancreatic and lung injury along with late liver injury in acute intoxication by Crotalaria retusa.
Sesame oil and peanut oil attenuated acute monocrotaline poisoning in our rat model. Peanut oil has been used as a local remedy for Crotalaria poisoning in cattle. Sesame oil and peanut oil attenuated pancreatic, lung, and liver injury in acute monocrotaline poisoning. Sesame oil efficiently decreased steatosis, but peanut oil was ineffective. Steatosis is associated with long-term complications and risk factors, including diabetes mellitus, protein malnutrition, hypertension, and obesity in rats and humans; these conditions have profound adverse effects on the pancreas, liver, and heart. We conclude that sesame oil is more beneficial than peanut oil in attenuating multiple organ injury in acute Crotalaria poisoning. Furthermore, sesame oil is effective against drug- and chemical-induced organ injury.[38-42] Sesame oil contains palmitic acid (8.58%), stearic acid (5.44%), and acids with a small amount of arachidic acid (0.9%), and its main unsaturated fatty acids are linoleic acid (46.26%) and oleic acid (38.84%). In addition, it contains phenol, sesamin, sesamol, sesamolin, and a relatively small amount of tocopherol, which contributes to its oxidative stability. In contrast, peanut oil is composed of approximately 80% unsaturated fatty acids with palmitic acid (7–11%), stearic acid (2–4%), oleic acid (48–54%), linoleic acid (27–38%), linolenic acid (0.62–1.12%), and arachidic acid (1.44–2.36%). Sesamol is a phenolic nonfat potent antioxidant; its rapid absorption (within 1 hour), distribution and metabolism (1 hour), and elimination (4–8 hours) without accumulation[45-47] indicate its versatile nature for prophylactic and therapeutic use against various toxic models in rodents. Sesamol prophylactically and therapeutically attenuates multiple organ injury in various disease models.[27, 48-50] Whether or not SC injected sesamol is useful in attenuating acute Crotalaria poisoning in cattle still is unknown. More investigation is needed.
Sesame oil is known to be harmless when taken in recommended dosages against oxidative stress-associated hepatic injury after cecal ligation and puncture in rats. When taken in a large dose, it does not have a cumulative antioxidative effect; instead its antioxidative effect is decreased. In addition, dietary fat with polyunsaturated fatty acid contributes to steatohepatitis. Hepatic metabolism of fat[52, 53] and monocrotaline requires cytochrome P-450 isozymes. A higher dose of oral sesame oil and peanut oil may contribute to steatohepatitis as well as affect metabolism and elimination of monocrotaline. An increased burden on liver metabolism as well as overall stress may be the reason for the increases in ALT and AST activity in Group IV and VI rats.
The implication of the present study is that it can be extrapolated to cattle pyrrolizidine alkaloid toxicosis. However, additional studies are needed. In addition, no definitive treatment for pyrrolizidine alkaloid toxicosis exists. Treatment consists of supportive care to allow time for liver regeneration and restoration of liver function. Supportive care includes administering IV fluid to correct dehydration and electrolyte abnormalities, glucose to provide basic energy requirements, and antibiotics to prevent infection. Local remedies include certain herbs. Veterinary teams that consist of a veterinarian, credentialed veterinary technician or veterinary technologist specialist, veterinary assistant, and certified veterinary practice manager usually administer groundnut or palm oil, atropine sulfate, or other antidiarrheal agents.[12, 54-56] Ruminants have 4-chamber stomachs with strong digestive and absorptive power. The abomasal compartment corresponds to the stomach of the nonruminant, and it secretes gastric juice with a pH range from 2.0 to 2.5. This low pH may facilitate breakdown of fatty acids in sesame oil and enhance absorption when given PO. Prophylactic and therapeutic SC injection of sesame oil attenuates acute renal injury in mice model. Subcutaneous injection of sesame oil may be effective in treating organ injury in cattle. Sesame oil was therapeutically effective for treating pancreatic, lung, and liver injury caused by monocrotaline poisoning in our rat model. Despite sesame oil's potent therapeutic effect against acute monocrotaline poisoning in rats, its use in cattle requires additional investigation.