Page 1043 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Cottonseed Toxicity Chapter | 68 975

VetBooks.ir incidence of pneumonia is also associated with acute gos- Disruption of Reproduction
sypol disease. Poisoning in pigs may result in reduced
Gossypol exposure adversely affects both male and
weight gain, anorexia, respiratory distress/thumping, car-
diac insufficiency, coughing, exercise intolerance, fluid female fertility as well as embryogenesis. In males, the
undoubted adverse effects of gossypol on the testis and
accumulation in body cavities, edema and congestion in
spermatogenesis have been mostly explored in rats, mice,
liver, lung, and spleen and cardiomyopathy and cardiac
hamsters, rabbits, monkeys, and humans (selected studies
hypertrophy (Fombad and Bryant, 2004).
summarized in Table 68.3). Gossypol has antifertility
effects in male rats at about 30 mg/kg where has humans
are approximately 100 times more sensitive with antifer-
Anemia tility effects being noted at 0.3 mg/kg (Coutinho, 2002).
Antifertility effects in humans are compounded by hypo-
Reduced hematocrit and hemoglobin are sensitive markers
kalemia and possibly irreversible sterilization or a slow
of excessive dietary gossypol (Table 68.2). The effects
recovery pattern. The modes of action of gossypol’s effect
may be due to iron deficient anemia due to gossypol com-
on male fertility are incompletely understood. Known
plexation of iron in the gut and alterations in iron utiliza-
effects include: (1) inhibition of release and utilization of
tion (Braham et al., 1967; Clawson et al., 1975; Randel
ATP by spermatocytes; (2) effects on microtubular func-
et al., 1996; Lindsey et al., 1980; Zhang et al., 2007;
tion; (3) inhibition of calcium influx; (4) ultrastructural
Mena et al., 2004; Skutches et al., 1973). However, gos-
damage to the nuclear membrane, endoplasmic reticulum
sypol also increases erythrocyte fragility and stimulates
and mitochondria; (5) DNA damage in Sertoli cells; and
eryptosis via a calcium-dependent mechanism (Zbidah
(6) reduction in androgen receptors in Leydig cells,
et al., 2012).
Sertoli cells, and myoid cells.
Selected studies on the effects of gossypol on female
reproduction are summarized in Table 68.4 Key effects
Hepatotoxicity on female reproduction include: (1) disruption of the
estrus cycle; (2) disruption of granulosa cell function; (3)
Hepatotoxicity is a noted effect in ruminants, pigs, rab-
disruption of ovarian follicle development; (4) inhibition
bits, dogs, cats, monkeys, poultry, and fish. A number of
of ovarian steroidogenesis; and (5) disruption of oocyte
species (notably sheep, swine, broiler chickens, rainbow
cumulus expansion and nuclear maturation.
trout, and catfish) display preferential accumulation of
Gossypol is known to disrupt embryonic development
gossypol in the liver (Alexander et al., 2008). Gossypol
and embryonic implantation (Gadelha et al., 2014). The
feeding of juvenile turbot (Scophthalmus maximus) was
mode of action of these effects is assumed to be direct
associated with a proinflammatory cytokine state, activa-
cytotoxicity, possibly in combination with oxidative
tion of the endoplasmic reticulum unfolded protein cellu-
stress, disruption of intercellular communication, and
lar stress response and hepatic fibrosis (Bian et al., 2016).
increased intracellular calcium. In vitro data demonstrates
Diffuse hepatocyte fatty change (severity was dose-
that in cattle, the critical window for gossypol exposure is
related), individual hepatocyte necrosis, perivascular lym-
at the one-cell stage of embryonic development
phoid aggregates were notable features in meat ducks
(Herna ´ndez-Cero ´n et al., 2005). Selected studies on the
exposed to dietary gossypol for up 14 days at levels that
effects of gossypol on embryonic development are sum-
resulted in impaired growth performance (Zeng et al.,
marized in Table 68.5.
2014). Dose-related hepatotoxicity, characterized by peri-
vascular lymphoid aggregate formation, biliary hyperpla-
sia, and hepatic cholestasis, occurred in chicks fed Undesirable Effects of Cottonseed
$ 400 mg of gossypol/kg (Henry et al., 2001). In calves, Meals on Eggs
gossypol-induced hepatotoxicity is characterized by cen-
trilobular hepatocellular necrosis (Holmberg et al., 1988; In general, cottonseed products should be used with cau-
Velasquez-Pereira et al., 1999). However, in preruminant tion in laying hens during egg production. There are two
calves, hepatotoxicity was characterized by periacinar main concerns, both of which involve egg discoloration.
necrosis in acute cases and periacinar fibrosis in chronic The first problem is that free gossypol is transferred from
cases (Zelski et al., 1995). Gossypol poisoning of dairy the hen to the eggs where it can combine with iron in the
goats was associated with acute centrilobular necrosis of egg yolk resulting in discoloration ranging from olive
the liver (East et al., 1994). Toxicity in pigs following green to brown to black. The yolk discoloration can be
ingestion of 1300 mg/kg of free gossypol featured marked extensive or focal (i.e., yolk mottling consisting of spots
centrilobular congestion, loss of hepatocytes, and fatty or blotches ranging in color from transparent to brownish
degeneration (Haschek et al., 1989). orange to almost black). The yolk color taint typically