Page 1037 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Cottonseed Toxicity Chapter | 68 969

VetBooks.ir of gossypol than PIMA varieties. Seeds from PIMA varie-
ties typically contain higher levels of the more toxic (2)
isomer ( 50%) compared with upland cotton varieties
( 40% (2)).

Dietary Bioavailability and Level of Exposure
Gossypol isomers exist in 2 states: bound and unbound
(covalent protein adducts, typically with lysine residues)
with the unbound form being the most toxicologically
active and the unbound form being mostly biologically
unavailable (Blasi and Drouillard, 2002; Gadelha et al.,
2014). Bound gossypol can be partially released by heat-
ing with acids. Maceration and rumen microflora actions
typically decrease the unbound bioavailable fraction due
to protein binding to ε-amino nitrogen, attaching to micro-
bial cell walls, and binding with iron (all forms of presys-
temic detoxification).
Extruding, grinding and cracking of whole cotton
seeds to improve digestibility may also increase the level
of unbound gossypol, particularly with PIMA varieties
(Blasi and Drouillard, 2002). These processes expose
more of the seed pigment glands to the rumen environ-
ment more quickly plus PIMA variety seeds typically
have fewer residual lint fibers and this tends to reduce
FIGURE 68.2 Sections of cottonseed showing darkly colored pigment their rumen residency time. This combination of effects
glands. Courtesy, Prof. K. S Rathore, Professor, Department of Soil & reduces rumen presystemic detoxification, thus increasing
Crop Sciences, IPGB Laboratory for Crop Transformation, Texas A&M toxic potential.
University.
Heating during the cottonseed meal manufacturing
process tends to increase the level of bound gossypol
polyhydroxylated aromatic aldehyde moieties. The two (Blasi and Drouillard, 2002), typically reducing the level
halves of the molecule may have different tautomeric of free gossypol to 0.1% 0.2%. The introduction of
forms resulting in multiple molecular species. This influ- expander-solvent technology (currently used in about
ences its chemical reactions. The gossypol molecule is 97% of cottonseed meal manufactured in the United
hindered around the bond connecting the two halves of States) in the manufacturing process has also resulted in a
the molecule thus the molecule is nonplanar and has a reduction of free gossypol levels by 50% compared
twofold axial dissymmetry. with typical levels in the 1960s and 1970s. Currently, cot-
Both gossypol stereoisomers typically both occur in tonseed hulls typically have less than 0.049% free gossy-
the plant, often with a slight predominance of the (1)-iso- pol content (Blasi and Drouillard, 2002). Improvements in
mer. However, upland cottons may have a 3:2 (1):(2) iso- mechanical and air separation techniques have reduced
mer ratio and some Gossypium sp. and commercial cotton the residual oil and protein levels in the hulls that are
varieties produce high levels (1) of isomer gossypol (e.g., important sources of gossypol. Pelleting can further
G. hirsutum var. marie produces about 82% (1)-gossy- reduce cottonseed hull gossypol levels.
pol). As a crude generalization, the (2) gossypol isomer is
reputedly more toxic than the (1) isomer (it is more cyto- TOXICOKINETICS
toxic, binds more strongly to proteins, it is the active anti-
spermatogenic agent, and it is generally more toxic; Dietary interactions with iron and rumen microfloral fer-
Alexander et al., 2008, Blasi and Drouillard, 2002). mentation can substantially reduce the systemic bioavail-
However, the (1) isomer is more slowly eliminated. ability of free gossypol. In rats, oral bioavailability is about
Cottonseeds contain about 0.4% 2% unbound gossy- 60% (Othman and Abou-Donia, 1988). Gossypol is often
pol (wt/wt) depending on species, variety, plant growth highly protein-bound to amino acids, particularly to those
conditions and level of insect predation (Blasi and rich in lysine. In rats, the volume of distribution is small fol-
Drouillard, 2002; Gadelha et al., 2014). Seeds from lowing IV dosing, implying limited distribution beyond the
upland cotton (G. hirsutum) typically contain lower levels plasma. The major sites of concentration are in the liver and