increment in the relative hepatic mRNA levels of c7 (complement component 7), a
gene involved in the innate immune system, was found (at 22 μg/L) [32].
The fish Rhamdia quelen was exposed to diclofenac at concentrations ranging
from 0 to 20 μg/L, and, as shown by Guiloski et al. [33], diclofenac reduced the
catalase and ethoxyresorufin-O-deethylase activities in fish exposed to 2 μg/L, in the
liver, and superoxide dismutase in all exposed groups; besides, the levels of reduced
glutathione and glutathione S-transferase activity increased at all tested concentrations, and lipid peroxidation was reduced (0.2 and 20 μg/L), but there was no protein
oxidation [33]. Diclofenac caused immune responses in gastropod species Lymnaea
stagnalis at environmental realistic (1–10 μg/L) and therapeutic (100–1,000 μg/L)
concentrations; the immune parameters of individual snails were measured: hemocyte density and viability, hemocyte phagocytosis capacity, and hemocyte-related
oxidative activities (basal and NADPH oxidase stimulated with zymosan particles)
[34]. The toxic effects of diclofenac were evaluated on Clarias gariepinus by acute
and chronic static renewable bioassay carried out by Ajima et al. [35]. Exposure to
acute toxicity resulted in abnormal behavior and mortality of some fish, but compared with the control, chronic exposure to 1.57, 3.14, and 6.28 mg/L showed
hematological alterations, including significantly higher mean corpuscular hemoglobin concentration, mean corpuscular volume, and white blood cell, with significantly
lower hemoglobin, hematocrit, red blood cell, and mean corpuscular hemoglobin
with increase in the concentration of the drug [35].
Cyprinus carpio is one of the most frequently bioindicators used to assess the
toxicological effects of NSAIDs on aquatic organisms. A study carried out by
Saucedo-Vence’s group showed that the exposure of Cyprinus carpio to median
lethal concentration of diclofenac caused alterations on the oxidative stress status in
the blood, muscle, gills, brain, and liver [36]. Islas-Flores et al. [37] evaluated the
toxicity induced by diclofenac, ibuprofen, and their mixture on Cyprinus carpio; the
results showed that diclofenac, ibuprofen, and a mixture of these pharmaceuticals
induced free radical production, oxidative stress, and cytogenotoxicity in tissues of
C. carpio, but a greater effect was elicited by the mixture than by either pharmaceutical alone in some biomarkers evaluated, particularly in the gill [37].
In order to assess the sub-chronic toxicity of naproxen, Cyprinus carpio was
exposed to 10, 50, 100, and 200 μg/L, and the results showed a strong effect on the
early life stages of the common carp. Besides, naproxen caused effects on hatching,
developmental rate, morphology, and histopathology [38]. Studies conducted to
evaluate the genotoxicity and cytotoxicity induced in the common carp using the
effluent emanating from a non-steroidal anti-inflammatory drug (NSAID)manufacturing plant, in Mexico, showed that carps exposed to the lowest observed
adverse effect level (LOAEL, 0.1173%) for 12, 24, 48, 72, and 96 h present a
significant positive correlations between NSAID concentrations and biomarkers of
geno- and cytotoxicity [39]. Besides, it was demonstrated that salicylic acid has
effects on the growth and development of common carp early life stages with respect
to antioxidant defense enzymes; in particular hatching, early ontogeny, and both
morphometric and condition characteristics were significantly influenced by
sub-chronic exposure to salicylic acid [40].
Overview of Non-steroidal Anti-inflammatory Drugs as Emerging Contaminants
47
gene involved in the innate immune system, was found (at 22 μg/L) [32].
The fish Rhamdia quelen was exposed to diclofenac at concentrations ranging
from 0 to 20 μg/L, and, as shown by Guiloski et al. [33], diclofenac reduced the
catalase and ethoxyresorufin-O-deethylase activities in fish exposed to 2 μg/L, in the
liver, and superoxide dismutase in all exposed groups; besides, the levels of reduced
glutathione and glutathione S-transferase activity increased at all tested concentrations, and lipid peroxidation was reduced (0.2 and 20 μg/L), but there was no protein
oxidation [33]. Diclofenac caused immune responses in gastropod species Lymnaea
stagnalis at environmental realistic (1–10 μg/L) and therapeutic (100–1,000 μg/L)
concentrations; the immune parameters of individual snails were measured: hemocyte density and viability, hemocyte phagocytosis capacity, and hemocyte-related
oxidative activities (basal and NADPH oxidase stimulated with zymosan particles)
[34]. The toxic effects of diclofenac were evaluated on Clarias gariepinus by acute
and chronic static renewable bioassay carried out by Ajima et al. [35]. Exposure to
acute toxicity resulted in abnormal behavior and mortality of some fish, but compared with the control, chronic exposure to 1.57, 3.14, and 6.28 mg/L showed
hematological alterations, including significantly higher mean corpuscular hemoglobin concentration, mean corpuscular volume, and white blood cell, with significantly
lower hemoglobin, hematocrit, red blood cell, and mean corpuscular hemoglobin
with increase in the concentration of the drug [35].
Cyprinus carpio is one of the most frequently bioindicators used to assess the
toxicological effects of NSAIDs on aquatic organisms. A study carried out by
Saucedo-Vence’s group showed that the exposure of Cyprinus carpio to median
lethal concentration of diclofenac caused alterations on the oxidative stress status in
the blood, muscle, gills, brain, and liver [36]. Islas-Flores et al. [37] evaluated the
toxicity induced by diclofenac, ibuprofen, and their mixture on Cyprinus carpio; the
results showed that diclofenac, ibuprofen, and a mixture of these pharmaceuticals
induced free radical production, oxidative stress, and cytogenotoxicity in tissues of
C. carpio, but a greater effect was elicited by the mixture than by either pharmaceutical alone in some biomarkers evaluated, particularly in the gill [37].
In order to assess the sub-chronic toxicity of naproxen, Cyprinus carpio was
exposed to 10, 50, 100, and 200 μg/L, and the results showed a strong effect on the
early life stages of the common carp. Besides, naproxen caused effects on hatching,
developmental rate, morphology, and histopathology [38]. Studies conducted to
evaluate the genotoxicity and cytotoxicity induced in the common carp using the
effluent emanating from a non-steroidal anti-inflammatory drug (NSAID)manufacturing plant, in Mexico, showed that carps exposed to the lowest observed
adverse effect level (LOAEL, 0.1173%) for 12, 24, 48, 72, and 96 h present a
significant positive correlations between NSAID concentrations and biomarkers of
geno- and cytotoxicity [39]. Besides, it was demonstrated that salicylic acid has
effects on the growth and development of common carp early life stages with respect
to antioxidant defense enzymes; in particular hatching, early ontogeny, and both
morphometric and condition characteristics were significantly influenced by
sub-chronic exposure to salicylic acid [40].
Overview of Non-steroidal Anti-inflammatory Drugs as Emerging Contaminants
47