CHS Nutrition: Alkaloid Toxicity in Range Cattle

Introduction
Most forage grasses are relatively free of toxic compounds that are dangerous to livestock. However, there are a few grasses such as tall fescue, perennial ryegrass, and reed canary grass that produce alkaloids through a mutual relationship with an endophytic fungus ('endo', meaning within, and 'phyte', meaning plant). Mutualism is an interaction existing between two organisms that is beneficial to both organisms. In this relationship, the endophytic fungus resides between the plant cells and gains soluble nutrients from photosynthesis by the plant. The plant derives many benefits from this mutualistic relationship with endophytic fungus, such as enhanced drought tolerance, increased growth, and resistance to grazing. The fungus appears to be transmitted by the seed only. Endophyte-infected temperate grasses appear to have negative effects on beef cattle and sheep performance, resulting in large economic losses to producers. The main reason for these negative effects appears to be alkaloids produced by endophytic fungi associated with these plants. The negative effects include heat intolerance, fat necrosis, fescue foot, decreased weight gains, ryegrass staggers, and death.

Tall Fescue
Tall fescue is a predominant cool-season, perennial grass introduced into North and South America from Europe in the mid-1800's. Tall fescue is an important turf and forage crop, cultivated on 29 to 35 million acres in the southern, Midwest, and northwest United States. As a cool-season grass, tall fescue is used in conjunction with warm-season grasses to supply forage to livestock during the cool times of the year. In 1993, 21 states were found to use tall fescue for hay and pasture, with an estimated 8.5 million cattle and 688,000 horses grazing tall fescue pastures. Tall fescue provides cattle with a good nutrient source in comparison to other grasses, providing 16% crude protein, 63% neutral detergent fiber, 6% ether extract (i.e., fats and oils) and 10% ash. However, tall fescue also contains an endophytic fungus that can have various adverse effects on cattle including inhibition of digestion, heat intolerance, fat necrosis, fescue foot, and decreased performance.

Alkaloids
Why do these problems exist? Researchers have concluded that these problems are caused by toxic alkaloids associated with the plant. Alkaloids are nitrogenous compounds produced by some organisms as a defense mechanism. The alkaloids in tall fescue are produced by an endophytic fungus associated with tall fescue and by the tall fescue plant itself.

Ergot Alkaloids
Alkaloids produced by fungus are termed ergot alkaloids. Ergot alkaloids produced by endophytic fungi include ergovaline, ergotamine, ergovine, lysergamine, and possibly others yet to be identified. All ergot alkaloids have similar effects on cattle but differ in their potency, with ergovaline being the most potent alkaloid identified in tall fescue. Ergot alkaloids have many adverse pharmacological effects on cattle, which are commonly termed "fescue toxicosis". Signs of fescue toxicosis include heat intolerance, fat necrosis, lameness, and associated decreased performance. Fescue toxicosis costs the U.S. beef industry about $609 million in losses each year. Therefore, finding solutions to eliminate or reduce this problem should be a high priority.

Tall Fescue Alkaloids
Tall fescue also produces alkaloids independent of the endophytic fungus. Researchers have suggested that fescue alkaloids decrease the number of endophytes by inhibiting their growth. Others have suggested ruminal microorganisms might also be inhibited. Fescue alkaloids have also been implicated in decreasing palatability and intake because of bitterness. Voluntary intake of tall fescue increases with advancing maturity, which may be related to decreasing concentrations of fescue alkaloids with increasing plant maturity. However, compared to ergot alkaloids, fescue alkaloids have mild effects on beef cattle.

Fescue Toxicosis Symptoms
The negative effects of fescue alkaloids can be severe but management strategies can be implemented to lessen their effects. The first step to mitigating the problems caused by endophyte-infected tall fescue is an understanding of the symptoms of fescue toxicosis.

Symptom #1: Heat intolerance. Heat intolerance is the inability of animals to adjust to increased ambient temperatures. Heat intolerance affects the majority of the herd when temperatures exceed 86° F. Outward signs of heat intolerance in cattle affected by fescue toxicosis include standing in water, excessive use of shade, and rough hair coats. The primary cause of heat intolerance appears to be vasoconstriction (blood vessel constriction) by ergot alkaloids. This vasoconstriction causes decreased blood flow to peripheral tissues, body core and brain. As a result, the animal loses its ability to dissipate heat through the skin and ears. Increased respiration rates are often observed as animals seek alternative methods to dissipate heat. In addition, cortisol, a hormone produced in response to stress, also increases in the blood with increased intake of endophyte-infected tall fescue.
Symptom #2: Fat necrosis. Fat necrosis occurs when fat hardens and dies. Fat lesions are a deep yellow color compared to normal fat and often contain chalky white or orange colored areas. Fat necrosis occurs when blood flow to the body core decreases. Normal adipose cells fill with fat evenly but necrotic adipose cells show uneven filling of cells. Dead cells are usually found interspersed with healthy cells in necrotic fat lesions. These hard, necrotic lesions can cause constriction of intestines, reproductive problems, and kidney failure in cattle.
Symptom #3: Fescue foot. Probably the most well known negative effect associated with grazing endophyte-infected tall fescue is a condition known as "fescue foot". Researchers estimate 20% of a herd grazing endophyte-infected tall fescue will be affected with this condition. Early clinical signs of fescue foot may appear 3 to 7 days after cattle graze endophyte-infected fescue. These signs include a red line forming at the coronary band of the hind feet and skin discoloration and swelling, which will worsen if animals are allowed to remain grazing the fescue. Death of peripheral tissues can occur as a result of vasoconstriction and subsequent inadequate blood flow to the periphery. Fescue foot occurs more commonly in cool periods because cattle have normal vasoconstriction to conserve body heat compounded with vasoconstriction by ergot alkaloids. When lameness is first observed, cattle must be immediately removed from endophyte-infected tall fescue pastures and fed an alternative feed.
Symptom #4: Decreased production. Decreased production is the most costly adverse effect caused by endophyte-infected tall fescue. Decreased production can result in significant economic losses to the livestock producer, because of lower cow and calf weights at the end of the grazing season. In 1983, University of Georgia researchers studied the effect of endophyte-free versus endophyte-infected tall fescue on performance of beef steers. Results showed grazing days were increased by 175 days when grazing endophyte containing compared to endophyte-free tall fescue (768 and 593 days, respectively). However, they also found average daily gains and beef gain per acre were increased by grazing endophyte-free compared to endophyte-infected tall fescue. The authors concluded endophyte-free tall fescue provided superior feed for beef steers compared to endophyte-infected tall fescue. Other researchers have confirmed these results and further noted that endophyte-free fescue can be expected to yield cattle production similar to other popular forage grasses like orchard grass. Decreased calf weights have also been reported for calves grazing endophyte-infected compared to endophyte-free tall fescue and other forage grasses. Decreased weaning weights are caused in part by decreased milk consumption because cows grazing endophyte-infected fescue experience reduced milk production. Prolactin is a hormone secreted by the animal to initiate lactation by filling the mammary glands with milk and decreased milk production appears to be a result of decreased prolactin secretion in cows grazing endophyte-infected tall fescue.

Other Endophyte Infected Grasses
Tall fescue is by far the most important forage grass afflicted with endophytic fungi. However, several other grasses also produce alkaloids. These include perennial ryegrass, annual ryegrass, and reed canary grass. Perennial ryegrass produces the same alkaloids found in tall fescue and additional alkaloids associated with a mutualistic endophyte. The endophyte of perennial ryegrass has been shown to increase growth, density, and insect resistance compared to endophyte-free ryegrass varieties. The alkaloids in perennial ryegrass produce involuntary convulsing when animals are excited or disturbed, a condition known as 'ryegrass staggers'. Ryegrass staggers are more common in warm, drought conditions in heavily grazed pastures. Severe outbreaks have resulted in substantial livestock losses with the greatest loss in young lambs as a result of depressed lactation. Heat stress, depressed weight gains, and reduced serum prolactin have been observed in sheep grazing endophyte-infected perennial ryegrass. Alkaloids are also produced in association with an endophytic fungus residing in annual ryegrass, however toxicosis is only seen in annual ryegrass parasitized by a nematode. The toxins are produced by a bacterium associated with the nematode that yields a yellow slime on the seed heads. Toxicosis may appear as soon as two days or as late as 12 weeks after grazing the toxic forage. Signs of toxicosis in sheep include a high stepping gait, lack of coordination, and convulsions. Signs are similar to ryegrass staggers but more death loss is associated with annual ryegrass toxicosis. Annual ryegrass staggers have also been reported in horses. Supplementing with cobalt in a mineral supplement appears to have some protective effects. Reed canarygrass is a grass well suited to poorly drained or flooded areas and low lying areas where spring melting snows or stream banks provide moist habitats. Alkaloids associated with reed canarygrass reduce grazing, can cause diarrhea, and reduce average daily gains. In sheep, these alkaloids can cause a nervous syndrome and sudden collapse. Affected animals appear frightened when approached. Signs have occurred within four hours of turnout, but usually are seen between 12 and 72 hours after exposure. The nervous syndrome usually occurs 2-3 weeks after turnout. Again, cobalt supplementation seems be beneficial. Signs of toxicosis in cattle include hock stiffness, dragging the hind feet, and tongue and lip dysfunction, which results in eating difficulty.

Management to Reduce Incidences
Pasture and Animal Management Feed fescue in combination with other forages including Bermudagrass or clovers. The major problem associated with dilution with clovers is that the opportunity for utilizing clover varies greatly among regions. Clovers are sensitive to viruses and other diseases and they are comparatively shallow rooted and consequently subject to summer drought stress. Although research is limited, it appears that increased stocking rates on endophyte-infected tall fescue may improve animal performance and production. Increased stocking rates may decrease the formation of seed heads, which is where the majority of the endophytes reside. Friendly endophytes. In the near future, endophyte-infected cultivars containing non-toxic endophytes will be commercially available. Limited research suggests they will improve animal productivity; however, effects on stand persistence are unknown. Withdraw pregnant mares from endophyte-infected tall fescue pastures at least 30 to 60 days before their expected foaling date to reduce foaling problems. Hay Treatment and Dietary Additives Ammoniation of fescue hay has resulted in consistent improvement in animal performance. Energy supplementation with concentrated feedstuffs like grains and molasses-based feeds may overcome some of the negative effects of alkaloid containing grass forages. Mineral supplementation with selenium, copper, or cobalt have improved animal resistance to alkaloids in some cases but not given consistent results. Ensiling has been proposed as a way to mitigate the negative effects of fescue alkaloids, but limited research suggests it is not effective.

Pharmacologic Compounds
Ivermectin, a treatment for internal parasites, appears to have some positive effect for animals grazing alkaloid-containing grasses. The specific mode of action and method of administration have not been fully researched. Domperidone, a dopamine agonist, appears to be an effective treatment for fescue toxicosis in horses and may soon be commercially available.

Managing the Effects of Alkaloid Toxicity in Range Cattle