The experimental groups of Galar-Martínez et al. [41] and Pérez-Coyotl [42],
using C. carpio as bioindicator, evaluated the oxidative stress and genotoxicity
induced by sub-lethal concentrations of ketorolac (1 and 60 μg/L) in the liver,
brain, and blood as well as the genotoxicity and cytotoxicity induced in the blood,
liver, and gill of C. carpio by the pollutants present in a water reservoir. Ketorolac
induced oxidative damage (increased lipid peroxidation, hydroperoxide content, and
protein carbonyl content) and changes in antioxidant status (superoxide dismutase,
catalase, and glutathione peroxidase activity) in the liver and brain of carp, and in the
blood, ketorolac increased the frequency of micronuclei and is therefore genotoxic
for the test species. On the other hand, the water reservoir caused significant
increases in all biomarkers in all tissues evaluated (DNA damage, frequency of
micronuclei, apoptosis, and caspase-3 activity) [41, 42].
Another bioindicator using frequently for evaluation of toxic effects of NSAIDs
is Danio rerio. Exposure of adult zebrafish (Danio rerio) to naproxen caused
moderate effects on the expression of antioxidant genes in the intestine rather than
in the liver, including Ucp-2 at 1 μg/L, and an increased expression of GST p2 at
100 μg/L, demonstrating that the intestine is more sensitive than the liver [43]. van
den Brandhof and Montforts [44], using a fish embryo toxicity (FET) test, evaluated
the effects of diclofenac and metoprolol on Danio rerio, finding specific effects on
hatching, yolk sac, and tail deformation above 1.5 mg/L for diclofenac and on
scoliosis and growth retardation above 12.6 mg/L for metoprolol [44]. On the
other hand, Li et al. [45] obtained the values of 96-h LC 50 of 115.2 mg/L for
embryos and 147.6 mg/L for larvae indicating that zebrafish embryos were more
sensitive than larvae to naproxen exposure and naproxen-treated zebrafish larvae
exhibited histopathological liver damage, including swollen hepatocytes, vacuolar
degeneration, and nuclei pyknosis, indicating that naproxen is a potential threat to
aquatic organisms [45].
The exposition of juvenile zebrafish to salicylic acid at concentrations of 0.004,
0.04, 0.4, 4, and 40 mg/L caused no effects on histological changes, specific growth
rate glutathione reductase, and lipid peroxidation but increased the catalytic activity
of GPx (at 0.04 mg/L) catalase (at 0.04 and 4 mg/L) and glutathione-S-transferase
(at 0.004 and 0.04 mg/L) compared to controls [46]. Moreover, Danio rerio was
exposed to naproxen (0.1, 1, 10, and 100 μg/L) and its thyroid-disrupting effects
were evaluated. Xu et al. [47] showed that naproxen caused a decrease of cytochrome P450 gene expression and enzyme activity might inhibit its metabolism
which might resulted in the significant bioconcentration; besides, both triiodothyronine and thyroxine levels were substantially decreased; thus, thyroid disruption
should be considered when assessing the aquatic risk of long-term exposure to
environmentally relevant concentrations [47]. Also, adult zebrafish, of both sexes,
were exposed to NSAIDs such as atenolol, ketoprofen, and diclofenac, and their UV
photolysis products resulted more toxic than the parental compounds, causing an
increase in GST, MDA, and CAT levels [48].
Amphibians represent particularly vulnerable organisms, and many populations
around the world are currently at risk of extinction. Limnodynastes peronii were
exposed to a mixture of the common pharmaceutical contaminants including
48
A. Mejía-García et al.
using C. carpio as bioindicator, evaluated the oxidative stress and genotoxicity
induced by sub-lethal concentrations of ketorolac (1 and 60 μg/L) in the liver,
brain, and blood as well as the genotoxicity and cytotoxicity induced in the blood,
liver, and gill of C. carpio by the pollutants present in a water reservoir. Ketorolac
induced oxidative damage (increased lipid peroxidation, hydroperoxide content, and
protein carbonyl content) and changes in antioxidant status (superoxide dismutase,
catalase, and glutathione peroxidase activity) in the liver and brain of carp, and in the
blood, ketorolac increased the frequency of micronuclei and is therefore genotoxic
for the test species. On the other hand, the water reservoir caused significant
increases in all biomarkers in all tissues evaluated (DNA damage, frequency of
micronuclei, apoptosis, and caspase-3 activity) [41, 42].
Another bioindicator using frequently for evaluation of toxic effects of NSAIDs
is Danio rerio. Exposure of adult zebrafish (Danio rerio) to naproxen caused
moderate effects on the expression of antioxidant genes in the intestine rather than
in the liver, including Ucp-2 at 1 μg/L, and an increased expression of GST p2 at
100 μg/L, demonstrating that the intestine is more sensitive than the liver [43]. van
den Brandhof and Montforts [44], using a fish embryo toxicity (FET) test, evaluated
the effects of diclofenac and metoprolol on Danio rerio, finding specific effects on
hatching, yolk sac, and tail deformation above 1.5 mg/L for diclofenac and on
scoliosis and growth retardation above 12.6 mg/L for metoprolol [44]. On the
other hand, Li et al. [45] obtained the values of 96-h LC 50 of 115.2 mg/L for
embryos and 147.6 mg/L for larvae indicating that zebrafish embryos were more
sensitive than larvae to naproxen exposure and naproxen-treated zebrafish larvae
exhibited histopathological liver damage, including swollen hepatocytes, vacuolar
degeneration, and nuclei pyknosis, indicating that naproxen is a potential threat to
aquatic organisms [45].
The exposition of juvenile zebrafish to salicylic acid at concentrations of 0.004,
0.04, 0.4, 4, and 40 mg/L caused no effects on histological changes, specific growth
rate glutathione reductase, and lipid peroxidation but increased the catalytic activity
of GPx (at 0.04 mg/L) catalase (at 0.04 and 4 mg/L) and glutathione-S-transferase
(at 0.004 and 0.04 mg/L) compared to controls [46]. Moreover, Danio rerio was
exposed to naproxen (0.1, 1, 10, and 100 μg/L) and its thyroid-disrupting effects
were evaluated. Xu et al. [47] showed that naproxen caused a decrease of cytochrome P450 gene expression and enzyme activity might inhibit its metabolism
which might resulted in the significant bioconcentration; besides, both triiodothyronine and thyroxine levels were substantially decreased; thus, thyroid disruption
should be considered when assessing the aquatic risk of long-term exposure to
environmentally relevant concentrations [47]. Also, adult zebrafish, of both sexes,
were exposed to NSAIDs such as atenolol, ketoprofen, and diclofenac, and their UV
photolysis products resulted more toxic than the parental compounds, causing an
increase in GST, MDA, and CAT levels [48].
Amphibians represent particularly vulnerable organisms, and many populations
around the world are currently at risk of extinction. Limnodynastes peronii were
exposed to a mixture of the common pharmaceutical contaminants including
48
A. Mejía-García et al.