Ciprofloxacin affects the activity of glutathione S- transferase in different rat tissues
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EurAsian Journal of BioSciences
Eurasia J Biosci 14, 1983-1988 (2020)
Ciprofloxacin affects the activity of glutathione S-
transferase in different rat tissues
Kutayba F. Dawood 1*, Mohammed A. Jasim 2, Mohammed Oday Ezzat 3
1
Department of Chemistry, College of Education for Pure Sciences, University of Anbar, Ramadi, Anbar, IRAQ
2
Department of Biology, College of Education for Women, University of Anbar, Ramadi, Anbar, IRAQ
3
Department of Chemistry, College of Education for Women, University of Anbar, Ramadi, Anbar, IRAQ
*Corresponding author: eps.kutayba.farhan.dawood@uoanbar.edu.iq
Abstract
Glutathione S-transferases (GST) are multi-functional proteins involved in the detoxification of
xenobiotics and responsible for protecting cells against oxidative stress. The present study
investigated the inhibition effects of Ciprofloxacin on GST enzymes in the liver, renal, and pulmonary
tissues of the rat. Sixty Wistar rats were separated into 4 groups, 15 rats each (I–IV). Distilled water
was used for intraperitoneally injection of group I (control), however rats in other three groups (II, III,
and IV) were injected with 50mg/kg, 100mg/kg, and 150mg/kg of Ciprofloxacin, respectively. The
inhibitory effects of the Ciprofloxacin doses were evaluated after 2, 4 and 6 hours. The activity of
GST enzyme was significantly inhibited in response to Ciprofloxacin doses at different periods and
tissues (pEurAsian Journal of BioSciences 14: 1983-1988 (2020) Dawood et al.
Table 1. Impact of Ciprofloxacin antibiotic at different doses on GST activities of the liver,
kidney, and lung rat tissue time-dependently
P- value
Time (hour) Group I (Control) Group II Group III Group IV
(intra-group)
Liver GST Level (U/g protein)
2 3.082 ± 0.090 3.246 ± 0.148aA 2.656 ± 0.051aB 2.386 ± 0.061aC 0.001
4 3.024 ± 0.064 2.572 ± 0.240bA 1.760 ± 0.177bB 1.242 ± 0.069bC 0.001
6 2.926 ± 0.057 2.208 ± 0.085cA 1.182 ± 0.082cB 0.964 ± 0.113cC 0.001
P values (time-dependently) NS 0.001 0.001 0.001
Kidney GST Level (U/g protein)
2 2.272 ± 0.051 1.528 ± 0.117cB 1.920 ± 0.135bA 1.166 ± 0.159cC 0.001
4 2.176 ± 0.066 1.868 ± 0.113bA 0.914 ± 0.093cC 1.512 ± 0.095bB 0.001
6 2.170 ± 0.063 2.684 ± 0.108bB 2.512 ± 0.076cB 2.988 ± 0.100aA 0.001
P values (time-dependently) NS 0.001 0.001 0.001
Lung GST Level (U/g protein)
2 1.944 ± 0.030 2.138 ± 0.046bB 1.922 ± 0.107aC 2.206 ± 0.039aA 0.001
4 1.806 ± 0.054 1.506 ± 0.106cA 1.200 ± 0.125bB 0.754 ± 0.158cC 0.001
6 1.740 ± 0.049 2.524 ± 0.096aA 2.058 ± 0.089aB 1.116 ± 0.133bC 0.001
P values (time-dependently) NS 0.001 0.001 0.001
a, b, c (pEurAsian Journal of BioSciences 14: 1983-1988 (2020) Dawood et al.
Fig. 3. The effect of different doses of Ciprofloxacin on lung
Fig. 1. The effect of Ciprofloxacin with different doses on tissue GST enzyme activities
GST enzyme activities of hepatic tissues
They are playing a vital role in multiple regulations of
biological and physiological activities as important
signaling molecules. But, ROS produced by oxidative
stress may inflict intense damage to cell lipids, proteins,
and nucleic acids (Jia et al. 2020). In normal conditions,
antioxidants serve in cell protection against ROS-
mediated oxidative damages (Snezhkina et al. 2020). As
a consequence, Various diseases such as cancer,
diabetes, chronic kidney disease, and cardiovascular
diseases will possibly be induced. Therefore,
biomarkers of oxidative stress may be helpful as a
diagnostic tool or therapeutics (Oraby and Rabie 2020).
A typical antioxidant enzyme, Glutathione S-
transferase a versatile key enzyme and effectively
participating in drug metabolism, as well as
Fig. 2. The effects of three different doses of Ciprofloxacin detoxification of endogenous and/or exogenous
on kidney tissue GST enzyme activities compounds like ROS and xenobiotics (Fujitani et al.
2019). Low activity of antioxidant enzymes as GST has
between the second (II) and fourth (IV) groups were a decisive role in host defense mechanisms against
inactivated within the first two hours. Interestingly, the infection by up-regulating oxidative defense
investigated enzyme showed an improved activity in mechanisms (Sohail et al. 2007).
other intervals (pEurAsian Journal of BioSciences 14: 1983-1988 (2020) Dawood et al.
physiological function of enzymes and the exact depletion of GSH (Aniya et al. 1993). Consequently,
mechanism of the adverse effects of this drug (Bibi inhibition of GST activity found to be associated with the
2008). intracellular depletion of glutathione, approving drug
In this paper, we evaluated the in vivo effect of three toxicity. Additional studies have confirmed that the
doses of Ciprofloxacin on GST enzyme activity. In all rat fluoroquinolone can develop an oxidative damages and
groups treated with Ciprofloxacin, GST enzyme exhausting the antioxidant system (Aniya et al. 1993,
activities in the hepatic tissue were inhibited compared Talla and Veerareddy 2011).
to the control group, in the III and IV groups starting at 2 Olayinka and co-authors evaluated the effect of two
hours, and in the II group at 4 hours. Moreover, this fluoroquinolones antibiotics (Levofloxacin and
inhibition continued even at the end of the 6th hour. Moxifloxacin) on rat tissue GST activity with different
Results indicated that the potent inhibitory effect of GST doses: all doses used caused a significant inhibition on
enzymes in liver tissue was observed after the 6th hour GST activity (Olayinka et al. 2015, Ore and Olayinka
and for all tested doses. 2015).
For renal tissues, GST enzyme activities were In conclusion, the current results reveal that the
inhibited in the animal treated groups (II-IV) from the 2nd different doses of Ciprofloxacin causes a critical drop in
hours to the end of the 4th hour period, while beginning GST activities in all tested tissues. In group IV,
to enhance in the next time. Significant inhibition of GST Ciprofloxacin (150 mg) showed the strongest inhibitory
activity was seen during the first two hours period in the effect on GST activity of pulmonary and hepatic tissues
IV groups and after 4th hour in the III group. But, a strong at 4th and 6th hours respectively compared to the control
inhibition of kidney GST enzyme activity in the III group group. Whereas, the strongest inhibition of kidney GST
was observed after 4 hours. enzyme activity was observed in group III (100 mg of
In rat pulmonary tissues, it was observed that the Ciprofloxacin) after 4 hours (pEurAsian Journal of BioSciences 14: 1983-1988 (2020) Dawood et al.
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