Page 483 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

450 SECTION | V Metals and Micronutrients

VetBooks.ir neurological syndrome of gait disorders is common and Shukla, 1978). Developmental studies involving the use
of laboratory animals have also detected subtle changes
indicative of Mn-induced injury to the extrapyramidal
in growth (decreased body weight in animals provided with
motor system in the brain.
Mn can have a damaging effect on many body organs, relatively high doses of Mn). These changes were observed
including the brain, liver, pancreas and reproductive system. both when the animals were exposed while in utero or post-
In addition to these well-established neurotoxic effects, Mn partum. In a developmental rat model of chronic Mn toxic-
has been extensively studied for its reproductive and devel- ity, administration of Mn in drinking water was associated
opmental effects. Evidence obtained from laboratory ani- with increased levels of iron, copper, selenium, and calcium
mals indicates that exposure to high levels of Mn may in various brain regions. The biochemical mechanisms
adversely affect sperm quality (Elbetieha et al., 2001; underlying the interaction between Mn and other minerals
Ponnapakkam et al., 2003a,b), cause decreased testicular are unclear. For further details on Mn-induced reproductive
weights (Laskey et al., 1982) and impair development of the and developmental effects, readers are referred to a recent
male reproductive tract. Impaired fertility was observed in publication (Milatovic et al., 2017).
male mice exposed to Mn in drinking water for 12 weeks at Several studies have also addressed gene expression
a daily dose level of 309 mg/kg/day, but not at doses changes in Mn-treated cells and animals and the complex
# 154 mg/kg/day (Elbetieha et al., 2001). Decreased sperm interaction of Mn with other minerals (Baek et al., 2004;
motility and sperm counts were observed in male CD-1 HaMai et al., 2006). Mn-induced expression changes were
mice after 43 days of exposure to manganese acetate noted in genes involved in inflammation, DNA replication
(4.6 9.6 mg/kg/day). But these doses did not impair the and repair. Recent work in nonhuman primates (Guilarte
ability of these males to impregnate unexposed females et al., 2008) detected Mn-induced brain gene expression
(Ponnapakkam et al., 2003a,b). Szakmary et al. (1995) changes associated mainly with genes affecting apoptosis,
reported that Mn did not result in any reproductive effect in protein folding and degradation, inflammation and axo-
the rabbit when exposed to 11, 22 or 33 mg/kg/day on nal/vesicular transport. Cumulative evidence has estab-
gestation days 6 20. In 13-week dietary studies, no gross or lished that Mn exposure induces signs and symptoms
histopathological lesions or organ weight changes were similar but not identical to Parkinson’s disease (Tuschl
observed in reproductive organs of rats fed up to 618 mg et al., 2013; Rutchik et al., 2012; O’Neal and Zheng,
Mn/kg/day or mice fed up to 1950 mg Mn/kg/day. 2015; Kwakye et al., 2015; Guilarte and Gonzales, 2015).
Many developmental toxicity studies in animals
exposedtoMnhavefocused on possible effects on DIAGNOSIS
reproductive and neurological functions. Animal studies
have shown that Mn exposure decreased the growth of Diagnosis of Mn deficiency and toxicity is based on quanti-
reproductive organs (preputial gland, seminal vesicle tative determination of Mn in biological specimens (body
and testes) (Gray and Laskey, 1980). Testes weights in tissue or fluid). Normal valuesofMninliver andkidneyare
males were significantly decreased from controls only reported in cattle (2.5 6.0 ppm and 1.2 2.0 ppm), horses
when Mn was administered in conjunction with an iron- (1.0 6.0 ppm and 0.5 2.4 ppm), sheep (2.0 4.4 ppm and
poor diet (Laskey et al., 1982). Studies in neonatal ani- 0.8 2.5 ppm), goats (2.0 6.0 ppm and 1.0 3.0 ppm), pigs
mals have detected structural and neurochemical changes (2.30 4.00 ppm and 1.30 2.0 ppm), dogs (3.0 5.0 ppm
at dosesofMnsimilarto orslightlyabove dietarylevels and 1.2 1.8 ppm) and rabbits (1.0 2.0 ppm and
(1 10 mg Mn/kg/day) (Chandra and Shukla, 1978; 2.0 3.0 ppm). Mn levels are also reported for blood
Deskin et al., 1980), suggesting that young animals in cattle (0.07 0.09 ppm), sheep (0.02 0.025 ppm), dogs
might be more susceptible to Mn than adults. Another (0.02 ppm), pigs (0.04 ppm) and poultry (0.085 0.091 ppm).
study by Dorman et al. (2000) also suggested that neona- From human studies it is indicated that neither blood nor
tal rats are at greater risk than adults for Mn-induced urinary Mn levels correlates with any neurological manifesta-
neurotoxicity when compared under similar exposure tions. Analysis is performed by Flame Atomic Absorption or
conditions. Their study showed that oral Mn exposure Furnace Atomic Absorption Spectrometer or Inductively
(11 or 22 mg/kg/day for 21 days) induced a significant Coupled Plasma (ICP)/ICP-Mass Spectrometer. It is worth
increase in amplitude of the acoustic startle reflex and mentioning that none of the methods distinguish between
an increase in striatal DA and 3,4-dihydroxyphenylacetic different oxidation states of Mn.
acid concentrations in neonates treated with high doses.
In a similar study, neonatal rats exposed to Mn (0.31 mg
TREATMENT
Mn/kg/day for 60 days in water) suffered neuronal
degeneration and increased brain monoamine oxidase on The very first step in the treatment of Mn poisoning
day 15 and 30 of the study, but did not show any clinical should be to remove the animals from any further
or behavioral signs of neurotoxicity (Chandra and exposure by avoiding contaminated feed, water or any other