Year 2022,
Volume: 12 Issue: 1, 155 - 161, 30.03.2022
Erdogan Karatas
Zafer Bayraktutan
,
Elif Çadırcı
References
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Atmaca HT, Kocak Ozgeris FB, et al. Paracetamol-induced
nephrotoxicity and oxidative stress in rats: the protective role
of Nigella sativa. Pharm Biol. 2016;54(10):2082-2091.
- [2] Agrawal S, Khazaeni B. Acetaminophen Toxicity. StatPearls.
Treasure Island (FL)2021.
- [3] Davidson DG, Eastham WN. Acute liver necrosis following
overdose of paracetamol. Br Med J. 1966;2(5512):497-499.
- [4] Bessems JG, Vermeulen NP. Paracetamol (acetaminophen)-
induced toxicity: molecular and biochemical mechanisms,
analogues and protective approaches. Crit Rev Toxicol.
2001;31(1):55-138.
- [5] Corcoran GB, Mitchell JR, Vaishnav YN, Horning EC. Evidence
that acetaminophen and N-hydroxyacetaminophen
form a common arylating intermediate, N-acetyl-parabenzoquinoneimine.
Mol Pharmacol. 1980;18(3):536-542.
- [6] Nguyen NU, Stamper BD. Polyphenols reported to shift APAPinduced
changes in MAPK signaling and toxicity outcomes.
Chem Biol Interact. 2017;277:129-136.
- [7] Kayaalp SO. Akılcı tedavi yönünden tıbbi farmakoloji: Pelikan
Yayıncılık; 2012 (Turkish).
- [8] Bulsara KG, Cassagnol M. Amlodipine. StatPearls. Treasure
Island (FL)2021.
- [9] Schrier RW, Arnold PE, Van Putten VJ, Burke TJ. Cellular calcium
in ischemic acute renal failure: role of calcium entry blockers.
Kidney Int. 1987;32(3):313-321.
- [10] Albayrak A, Bayir Y, Halici Z, Karakus E, Oral A, Keles MS. The
biochemical and histopathological investigation of amlodipine
in ethylene glycol-induced urolithiasis rat model. Ren Fail.
2013;35(1):126-131.
- [11] Coskun AK, Gunal A, Halici Z, Oral A, Seyrek M, Bayir Y. The
effects of amlodipine on the biochemical and histopathological
changes in the rabbit ileum subjected to ischemia-reperfusion.
Eurasian J Med. 2011;43(1):33-38.
- [12] Halici Z, Karaca M, Keles ON, Borekci B, Odabasoglu F, Suleyman
H. Protective effects of amlodipine on ischemia-reperfusion
injury of rat ovary: biochemical and histopathologic evaluation.
Fertil Steril. 2008;90(6):2408-2415.
- [13] Suleyman H, Halici Z, Hacimuftuoglu A, Gocer F. Role of adrenal
gland hormones in antiinflammatory effect of calcium channel
blockers. Pharmacol Rep. 2006;58(5):692-699.
- [14] Chattopadhyay RR. Possible mechanism of hepatoprotective
activity of Azadirachta indica leaf extract: part II. J
Ethnopharmacol. 2003;89(2-3):217-219.
- [15] Sun Y, Oberley LW, Li Y. A simple method for clinical assay of
superoxide dismutase. Clinical Chemistry 1988;34(3):497-500.
- [16] Sedlak J, Lindsay RH. Estimation of total, protein-bound, and
nonprotein sulfhydryl groups in tissue with Ellman’s reagent.
Analytical Biochemistry 1968; 25(1):192-205.
- [17] Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal
tissues by thiobarbituric acid reaction. Analytical Biochemistry
1979;95(2):351-358.
- [18] Bayir Y, Un H, Cadirci E, Akpinar E, Diyarbakir B, Calik I. Effects
of Aliskiren, an RAAS inhibitor, on a carrageenan-induced
pleurisy model of rats. Anais da Academia Brasileira de
Ciências 2019;91(1): e20180106.
- [19] Karaoglan ES, Bayir Y, Albayrak A, Toktay E, Ozgen U, Kazaz C.
Isolation of Major Compounds and Gastroprotective Activity
of Alchemilla Caucasica on Indomethacin Induced Gastric
Ulcers in Rats. Eurasian J Med. 2020;52(3):249-253.
- [20] Un H, Ugan RA, Kose D, Bayir Y, Cadirci E, Selli J. A novel effect
of Aprepitant: Protection for cisplatin-induced nephrotoxicity
and hepatotoxicity. Eur J Pharmacol. 2020;880:173168.
- [21] Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman &
Gilman’s the pharmacological basis of therapeutics: McGraw-
Hill Education New York; 2018.
- [22] Ozkaya O, Genc G, Bek K, Sullu Y. A case of acetaminophen
(paracetamol) causing renal failure without liver damage in a
child and review of literature. Renal Failure 2010;32(9):1125-
1127.
- [23] Prescott LF. Paracetamol overdosage-Pharmacological
considerations and clinical management. Drugs
1983;25(3):290-314.
- [24] Mazer M, Perrone J. Acetaminophen-induced nephrotoxicity:
pathophysiology, clinical manifestations, and management. J
Med Toxicol. 2008;4(1):2-6.
- [25] El-Sayed EM, Abd-Allah AR, Mansour AM, El-Arabey AA.
Thymol and carvacrol prevent cisplatin-induced nephrotoxicity
by abrogation of oxidative stress, inflammation, and apoptosis
in rats. J Biochem Mol Toxicol. 2015;29(4):165-172.
- [26] Somchit MN, Sanat F, Hui GE, Wahab SI, Ahmad Z. Mefenamic
Acid induced nephrotoxicity: an animal model. Adv Pharm
Bull. 2014;4(4):401-404.
- [27] Naguib YM, Azmy RM, Samaka RM, Salem MF. Pleurotus
ostreatus opposes mitochondrial dysfunction and oxidative
stress in acetaminophen-induced hepato-renal injury. BMC
Complement Altern Med. 2014;14:494.
- [28] Das J, Ghosh J, Manna P, Sil PC. Taurine protects
acetaminophen-induced oxidative damage in mice kidney
through APAP urinary excretion and CYP2E1 inactivation.
Toxicology. 2010;269(1):24-34.
- [29] Li J, Tie CR, Li QX, Zheng F. Amlodipine prevents adriamycininduced
toxicity in cultured rat mesangial cells by upregulation
of Smad6, Smad7 expression. Environ Toxicol Phar.
2014;38(1):251-256.
- [30] Tan H, Gepdiremen A, Halici Z. Effect of lithium and valproic
acid on kainate-induced neurotoxicity in cerebral cortical cell.
Asian J Chem. 2009;21(3):1769-1774.
- [31] Albayrak A, Bayir Y, Halici Z, Karakus E, Oral A, Keles MS. The
biochemical and histopathological investigation of amlodipine
in ethylene glycol-induced urolithiasis rat model. Febs J.
2013;280(S1):336-337.
- [32] Abdul Hamid Z, Budin SB, Wen Jie N, Hamid A, Husain K,
Mohamed J. Nephroprotective effects of Zingiber zerumbet
Smith ethyl acetate extract against paracetamol-induced
nephrotoxicity and oxidative stress in rats. J Zhejiang Univ Sci
B. 2012;13(3):176-785.
- [33] Cominacini L, Fratta Pasini A, Garbin U, Pastorino AM, Davoli A,
Nava C, et al. Antioxidant activity of different dihydropyridines.
Biochem Biophys Res Commun. 2003;302(4):679-84. 176-185.
- [34] Liu LL, Li QX, Xia L, Li J, Shao L. Differential effects of
dihydropyridine calcium antagonists on doxorubicin-induced
nephrotoxicity in rats. Toxicology. 2007;231(1):81-90.
- [35] Nielsen F, Mikkelsen BB, Nielsen JB, Andersen HR, Grandjean
P. Plasma malondialdehyde as biomarker for oxidative stress:
Reference interval and effects of life-style factors. Clin Chem.
1997;43(7):1209-1214.
- [36] Aycan IO, Tokgoz O, Tufek A, Alabalik U, Evliyaoglu O, Turgut
H. The use of thymoquinone in nephrotoxicity related to
acetaminophen. Int J Surg. 2015;13:33-37.
- [37] Palabiyik SS, Karakus E, Halici Z, Cadirci E, Bayir Y, Ayaz G. The
protective effects of carvacrol and thymol against paracetamolinduced
toxicity on human hepatocellular carcinoma cell lines
(HepG2). Hum Exp Toxicol. 2016;35(12):1252-1263.
Investigation of the Effects of Amlodipine on Paracetamol- Induced Acute Kidney Toxicity in Rats
Year 2022,
Volume: 12 Issue: 1, 155 - 161, 30.03.2022
Erdogan Karatas
Zafer Bayraktutan
,
Elif Çadırcı
Abstract
Objective: Paracetamol is an analgesic and antipyretic agent that widely used throughout the world. The increase of the usage and its easy accessibility brings along the toxicity risk. Paracetamol toxicity may result in drug induced hepatotoxicity and nephrotoxicity. Anti-inflammatory and antioxidant effects of amlodipine which creates vasodilatation by blocking L-type calcium channels and its usage in elderly for renoprotective purposes, ponders that it might be favorable in cases with inflammation such renal damage inducted with paracetamol. Thus, aim of our study is to analyze effects of amlodipine, one of L-type calcium channel blockers, in acute renal damage inducted with paracetamol.
Methods: 30 male rats consisting of 5 groups were used in our study. Groups; I: Health Control group. 2 ml Phosphate-buffered saline (PBS) oral was administered. II: 10 mg/kg Amlodipine III: Paracetamol (2g/kg) IV: 5 mg/kg Amlodipine + paracetamol V: 10 mg/kg Amlodipine + paracetamol. Rats were sacrificed after 24 hours following paracetamol administration.
Results: Serum levels of creatinine and blood urea nitrogen (BUN) were increased in paracetamol group, those parameters improved in amlodipine groups. While superoxide dismutase (SOD) activity and glutathione (GSH) levels measured in kidney decreased in paracetamol group, amlodipine has significantly corrected these parameters. Meanwhile malondialdehyde (MDA) quantities increased in paracetamol group, it has been seen that in the amlodipine administered groups quantities of increased MDA have statistically significantly decreased
Conclusion: This study showed that amlodipine has protective effects against paracetamol toxicity in kidney. Amlodipine revealed its protective effects by suppressing the oxidative damage and improving antioxidant activity. Amlodipine can be drug of choice in hypertensive patients with analgesic nephropathies.
References
- [1] Canayakin D, Bayir Y, Kilic Baygutalp N, Sezen Karaoglan E,
Atmaca HT, Kocak Ozgeris FB, et al. Paracetamol-induced
nephrotoxicity and oxidative stress in rats: the protective role
of Nigella sativa. Pharm Biol. 2016;54(10):2082-2091.
- [2] Agrawal S, Khazaeni B. Acetaminophen Toxicity. StatPearls.
Treasure Island (FL)2021.
- [3] Davidson DG, Eastham WN. Acute liver necrosis following
overdose of paracetamol. Br Med J. 1966;2(5512):497-499.
- [4] Bessems JG, Vermeulen NP. Paracetamol (acetaminophen)-
induced toxicity: molecular and biochemical mechanisms,
analogues and protective approaches. Crit Rev Toxicol.
2001;31(1):55-138.
- [5] Corcoran GB, Mitchell JR, Vaishnav YN, Horning EC. Evidence
that acetaminophen and N-hydroxyacetaminophen
form a common arylating intermediate, N-acetyl-parabenzoquinoneimine.
Mol Pharmacol. 1980;18(3):536-542.
- [6] Nguyen NU, Stamper BD. Polyphenols reported to shift APAPinduced
changes in MAPK signaling and toxicity outcomes.
Chem Biol Interact. 2017;277:129-136.
- [7] Kayaalp SO. Akılcı tedavi yönünden tıbbi farmakoloji: Pelikan
Yayıncılık; 2012 (Turkish).
- [8] Bulsara KG, Cassagnol M. Amlodipine. StatPearls. Treasure
Island (FL)2021.
- [9] Schrier RW, Arnold PE, Van Putten VJ, Burke TJ. Cellular calcium
in ischemic acute renal failure: role of calcium entry blockers.
Kidney Int. 1987;32(3):313-321.
- [10] Albayrak A, Bayir Y, Halici Z, Karakus E, Oral A, Keles MS. The
biochemical and histopathological investigation of amlodipine
in ethylene glycol-induced urolithiasis rat model. Ren Fail.
2013;35(1):126-131.
- [11] Coskun AK, Gunal A, Halici Z, Oral A, Seyrek M, Bayir Y. The
effects of amlodipine on the biochemical and histopathological
changes in the rabbit ileum subjected to ischemia-reperfusion.
Eurasian J Med. 2011;43(1):33-38.
- [12] Halici Z, Karaca M, Keles ON, Borekci B, Odabasoglu F, Suleyman
H. Protective effects of amlodipine on ischemia-reperfusion
injury of rat ovary: biochemical and histopathologic evaluation.
Fertil Steril. 2008;90(6):2408-2415.
- [13] Suleyman H, Halici Z, Hacimuftuoglu A, Gocer F. Role of adrenal
gland hormones in antiinflammatory effect of calcium channel
blockers. Pharmacol Rep. 2006;58(5):692-699.
- [14] Chattopadhyay RR. Possible mechanism of hepatoprotective
activity of Azadirachta indica leaf extract: part II. J
Ethnopharmacol. 2003;89(2-3):217-219.
- [15] Sun Y, Oberley LW, Li Y. A simple method for clinical assay of
superoxide dismutase. Clinical Chemistry 1988;34(3):497-500.
- [16] Sedlak J, Lindsay RH. Estimation of total, protein-bound, and
nonprotein sulfhydryl groups in tissue with Ellman’s reagent.
Analytical Biochemistry 1968; 25(1):192-205.
- [17] Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal
tissues by thiobarbituric acid reaction. Analytical Biochemistry
1979;95(2):351-358.
- [18] Bayir Y, Un H, Cadirci E, Akpinar E, Diyarbakir B, Calik I. Effects
of Aliskiren, an RAAS inhibitor, on a carrageenan-induced
pleurisy model of rats. Anais da Academia Brasileira de
Ciências 2019;91(1): e20180106.
- [19] Karaoglan ES, Bayir Y, Albayrak A, Toktay E, Ozgen U, Kazaz C.
Isolation of Major Compounds and Gastroprotective Activity
of Alchemilla Caucasica on Indomethacin Induced Gastric
Ulcers in Rats. Eurasian J Med. 2020;52(3):249-253.
- [20] Un H, Ugan RA, Kose D, Bayir Y, Cadirci E, Selli J. A novel effect
of Aprepitant: Protection for cisplatin-induced nephrotoxicity
and hepatotoxicity. Eur J Pharmacol. 2020;880:173168.
- [21] Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman &
Gilman’s the pharmacological basis of therapeutics: McGraw-
Hill Education New York; 2018.
- [22] Ozkaya O, Genc G, Bek K, Sullu Y. A case of acetaminophen
(paracetamol) causing renal failure without liver damage in a
child and review of literature. Renal Failure 2010;32(9):1125-
1127.
- [23] Prescott LF. Paracetamol overdosage-Pharmacological
considerations and clinical management. Drugs
1983;25(3):290-314.
- [24] Mazer M, Perrone J. Acetaminophen-induced nephrotoxicity:
pathophysiology, clinical manifestations, and management. J
Med Toxicol. 2008;4(1):2-6.
- [25] El-Sayed EM, Abd-Allah AR, Mansour AM, El-Arabey AA.
Thymol and carvacrol prevent cisplatin-induced nephrotoxicity
by abrogation of oxidative stress, inflammation, and apoptosis
in rats. J Biochem Mol Toxicol. 2015;29(4):165-172.
- [26] Somchit MN, Sanat F, Hui GE, Wahab SI, Ahmad Z. Mefenamic
Acid induced nephrotoxicity: an animal model. Adv Pharm
Bull. 2014;4(4):401-404.
- [27] Naguib YM, Azmy RM, Samaka RM, Salem MF. Pleurotus
ostreatus opposes mitochondrial dysfunction and oxidative
stress in acetaminophen-induced hepato-renal injury. BMC
Complement Altern Med. 2014;14:494.
- [28] Das J, Ghosh J, Manna P, Sil PC. Taurine protects
acetaminophen-induced oxidative damage in mice kidney
through APAP urinary excretion and CYP2E1 inactivation.
Toxicology. 2010;269(1):24-34.
- [29] Li J, Tie CR, Li QX, Zheng F. Amlodipine prevents adriamycininduced
toxicity in cultured rat mesangial cells by upregulation
of Smad6, Smad7 expression. Environ Toxicol Phar.
2014;38(1):251-256.
- [30] Tan H, Gepdiremen A, Halici Z. Effect of lithium and valproic
acid on kainate-induced neurotoxicity in cerebral cortical cell.
Asian J Chem. 2009;21(3):1769-1774.
- [31] Albayrak A, Bayir Y, Halici Z, Karakus E, Oral A, Keles MS. The
biochemical and histopathological investigation of amlodipine
in ethylene glycol-induced urolithiasis rat model. Febs J.
2013;280(S1):336-337.
- [32] Abdul Hamid Z, Budin SB, Wen Jie N, Hamid A, Husain K,
Mohamed J. Nephroprotective effects of Zingiber zerumbet
Smith ethyl acetate extract against paracetamol-induced
nephrotoxicity and oxidative stress in rats. J Zhejiang Univ Sci
B. 2012;13(3):176-785.
- [33] Cominacini L, Fratta Pasini A, Garbin U, Pastorino AM, Davoli A,
Nava C, et al. Antioxidant activity of different dihydropyridines.
Biochem Biophys Res Commun. 2003;302(4):679-84. 176-185.
- [34] Liu LL, Li QX, Xia L, Li J, Shao L. Differential effects of
dihydropyridine calcium antagonists on doxorubicin-induced
nephrotoxicity in rats. Toxicology. 2007;231(1):81-90.
- [35] Nielsen F, Mikkelsen BB, Nielsen JB, Andersen HR, Grandjean
P. Plasma malondialdehyde as biomarker for oxidative stress:
Reference interval and effects of life-style factors. Clin Chem.
1997;43(7):1209-1214.
- [36] Aycan IO, Tokgoz O, Tufek A, Alabalik U, Evliyaoglu O, Turgut
H. The use of thymoquinone in nephrotoxicity related to
acetaminophen. Int J Surg. 2015;13:33-37.
- [37] Palabiyik SS, Karakus E, Halici Z, Cadirci E, Bayir Y, Ayaz G. The
protective effects of carvacrol and thymol against paracetamolinduced
toxicity on human hepatocellular carcinoma cell lines
(HepG2). Hum Exp Toxicol. 2016;35(12):1252-1263.