Efficacy of jamun Syzygium cumini seed and orange Citrus sinensis peel extracts against microcystin LR induced histological damage in the kidney of rat

Babita Deep Srivastava , Manish Srivastava , Makoto Urata , Nobuo Suzuki and Ajai Kumar Srivastav

Abstract
In this study we evaluated the protective effects of jamun Syzygium cumini seed and orange Citrus sinensis peel extracts on renotoxicity of microcystin LR in male rats. Groups A-F were given daily treatments for 30 days. Group A (Control): No treatment was given; Group B: microcystin (10 µg/kg body wt); Group C: microcystin (10 µg/kg body wt) and jamun seed extract (200 mg/kg body wt); Group D: microcystin (10 µg/kg body wt) and orange peel extract (200 mg/kg body wt; Group E: orange peel extract (200 mg/kg body wt); Group F: jamun seed extract (200 mg/kg body wt). Kidney were fixed at 15th and 30th day after the treatments. In 15 day MCLR (group B) treated rats shrunken glomeruli, hypertrophy of epithelial cells of tubules. vacuolation of cytoplasm and obliterated tubular lumina were noticed. In MCLR+JSE (group C) and MCLR+OPE (group D) treated rats almost similar changes were noticed as seen in MCLR treated rats. In OPE (group E) and JSE (group F) treated rats no visible morphological alterations were noticed. Following 30 day MCLR treatment (group B), increased cellularity of glomeruli, no space between the Bowman's capsule and glomerulus, glomerular degeneration, dilated tubules, separation of tubular epithelial cells from underlying basement membrane, tubular vacuolization and degeneration with necrotic nuclei in lumina and deposition of eosin-positive material in the tubules were observed. In MCLR+JSE (group C) and MCLR+OPE (group D) treated rats the glomeruli were swollen showing increased cellularity. No degeneration was noticed in glomeruli. Tubules were dilated, however, at few places few epithelial cells were degenerating. Necrotic nuclei were not seen in tubular lumina. In OPE (group E) and JSE (group F) treated rats the kidney exhibited no histological changes.

Keywords
Microcystin; Syzygium cumini; Citrus sinensis; Kidney; Cyanobacteria.

DOI
10.21472/bjbs(2020)071702

Full text
PDF

References
Abdel-Mageid, S. A. Structural changes in the kidney of albino rat in response to the administration of paraquat herbicide. Journal of Basic and Applied Zoology, v. 15, p. 153-175, 1994.

Abdel-Moneim, A. M.; Said, K. M. Acute effect of cadmium treatment on the kidney of rats: Biochemical and ultrastructural studies. Pakistan Journal of Biological Sciences, v. 10, p. 3497-3506, 2007. https://doi.org/10.3923/pjbs.2007.3497.3506

Afshar, S.; Farshid, A. A.; Heidari, R.; Llkhanipour, M. Histopathological changes in the liver and kidney tissues of Wistar albino rat exposed to fenitrothion. Toxicology and Industrial Health, v. 24, p. 581-586, 2008. https://doi.org/10.1177/0748233708100090

Al-Majeed, M. I. A.; Al-Sultan, E. Y. A.; Abbas, A. A. K. Toxic effects of low concentration of cyanotoxin (Microcystin-LR) on mice and study of protective efficacy of the antioxidants vitamins (C&aamp;E) and Capparis spinosa L. root extract. Journal of Natural Sciences Research, v. 6, p. 34-42, 2016.

Al-Mansour, M. I.; Al-Otaibi, N. M.; Alarifi, S. A.; Ibrahim, S. A.; Jarrar, B. M. Histological and histochemical alterations induced by lead in the kidney of the quail Coturnix coturnix. Toxicological & Environmental Chemistry, v. 91, no. 6, p. 1191-1203, 2009. https://doi.org/10.1080/02772240802590285

Al-Sultan, E. Y. A.; Al-Majeed, M. I. A.; Abbas, A. A. K. Study of physiological and histological effects under very low concentration of cyanobacterial toxin MC-LR on lab mice (Mus musculus). Research Journal of Pharmaceutical Biological and Chemical Sciences, v. 6, p. 1064-1072, 2015.

Amorim, A.; Vasconcelos, V. Dynamics of microcystins in the mussel Mytilus galloprovinvialis. Toxicon, v. 37, p. 1041-1052, 1999.

Ashraf, H.; Butt, M. S.; Iqbal, M. J.; Suleria, H. A. R. Citrus peel extract and powder attenuate hypercholesterolemia and hyperglycemia using rodent experimental modeling. Asian Pacific Journal of Troipical Biomedicine, v. 7, p. 870-880, 2017. https://doi.org/ 10.1016/j.apjtb.2017.09.012

Aslam, F.; Khan, A.; Khan, M. Z.; Sharaf, S.; Gul, S. T.; Saleemi, M. K. Toxico-pathological changes induced by cypermethrin in broiler chicks: Their attenuation with vitamin E and selenium. Experimental and Toxicologic Pathology, v. 62, p. 451-450, 2009. https://doi.org/10.1016/j.etp.2009.06.004

Atencio, L.; Moreno, I.; Prieto, A.; Moyano, R.; Molina, A. M.; Camean, A. M. Acute effects of microcystins MCLR and MCRR on acid and alkaline phosphatase activities and pathological changes in intraperitoneally exposed tilapia fish (Oreochromis sp.). Toxicologic Pathology, v. 36, p. 449-458, 2008. https://doi.org/10.1177/0192623308315356

Aughey, E.; Fell, G. S.; Scott, R.; Black, M. Histopathology of early effects of oral cadmium in rat kidney. Environmental Health Perspectives, v. 54, p. 153-161, 1984. https://doi.org/10.1289/ehp.8454153

Ayoola, S. O.; Ajani, E. K. Histopathological effects of cypermethrin on juvenile African catfish (Clarias gariepinusi). World Journal of Biological Research, v. 1, p. 1-14, 2008.

Barrouillet, M. P.; Potier, M.; Cambar, J. Cadmium nephrotoxicity assessed in isolated rat glomeruli and cultured mesanglial cells: Evidence for contraction of glomerular cells. Experimental Nephrology, v. 7, p. 251-258, 1999. https://doi.org/10.1159/000020610

Bashandy, S. A. E.; Ahmad-Farid, O. A. H.; Omara, E. A.; El-Toumy, S. A.; Salib, J. Y. Protective effects of Citrus reticulata peel extract against potassium dichromate-induced reproductive toxicity in rats. Asian Pacific Journal of Reproduction, v. 8, p. 267-275, 2019. https://doi.org/10.4103/2305-0500.270104

Bell, S. G.; Codd, G. A. Cyanobacterial toxins and human health. Reviews in Medical Microbiology, v. 5, p. 256-264, 1994.

Benson, J. M.; Hutt, J. A.; Rein, K.; Boggs, S. E.; Barr, E. B.; Fleming, L. E. The toxicity of microcystin LR in mice following 7 days of inhalation exposure. Toxicon, v. 45, p. 691-698, 2005. https://doi.org/10.1016/j.toxicon.2005.01.004

Brózman, O.; Kubickova, B.; Pavel B.; Petra, L. Microcystin-LR does not alter cell survival and intracellular signaling in human bronchial epithelial cells. Toxins, v. 12, no. 3, 165, 2020. https://doi.org/10.3390/toxins12030165

Brzoska, M. M.; Moniuszko-Jakoniuk, J.; Pilat-Marcinkiewicz, B.; Sawicki, B. Liver and kidney function and histology in rats exposed to cadmium and ethanol. Alcohol Alkoholism, v. 38, p. 2-10, 2003. https://doi.org/10.1093/alcalc/agg006

Calabro, M. L.; Galtieri, V.; Cutroneo, P.; Tommasini, S.; Ficara, R. Study of the extraction procedure by experimental design and validation of a LC method for determination of flavonoids in Citrus bergamia juice. Journal of Pharmaceutical and Biomedical Analysis, v. 35, p. 349-363, 2004.

Carmichael, W. W. Cyanobacteria secondary metabolites: The cyanotoxins. Journal of Applied Bacterialogy, v. 72, p. 445-459, 1992. https://doi.org/10.1111/j.1365-2672.1992.tb01858.x

Cengiz, E. I. Gill and kidney histopathology in the freshwater fish Cyprinus carpio after acute exposure to deltamethrin. Environmental Toxicology and Pharmacology, v. 22, p. 200-204, 2006. https://doi.org/10.1016/j.etap.2006.03.006

Chagas, V. T.; Coelho, R. M. R. S.; Gaspar, R. S.; Silva, S. A.; Mastrogiovanni, M.; Mendoca, C. J.; Ribeiro, M. N. S.; Paes, A. M. A.; Trostchansky, A. Protective effects of a polyphenol-rich extract from Syzygium cumini (L.) skeels leaf on oxidative stress-induced diabetic rats. Oxidative Medicine and Cellular Longevity, v. 2018, Article ID 5386079, 2018. https://doi.org/10.1155/2018/5386079

Colle, A.; Grimaud, J. A.; Boucherat, M.; Manuel, Y. Lead poisoning in monkeys: Functional and histopathological alterations of the kidneys. Toxicology, v. 18, p. 145-158, 1980. https://doi.org/10.1016/0300-483x(80)90077-3

Damain, F.; Frank, H.; Win Fried, M.; Hartmut, M.; Laus, W. Failure of radiotherapy to resolve fatal lung damage due to paraquat poisoning. Chest, v. 100, p. 1146-1165, 1992.

Dias, E.; Mariana, A.; Elsa, A.; Paulo, P.; Batoreu, M. C. C.; Jordan, P.; Silva, M. J. Comparative study of the cytotoxic effect of microcistin-LR and purified extracts from Microcystis aeruginosa on a kidney cell line. Toxicon, v. 53, p. 487-495, 2009. https://doi.org/10.1016/j.toxicon.2009.01.029

Elleman, T. C.; Falconer, I. R.; Jackson, A. R. B.; Runnegar, M. T. Isolation, characterization, and pathology of the toxin from a Microcystis aeruginosa (= Anacystis cyanea) bloom. Australian Journal of Biological Sciences, v. 31, p. 209-218, 1978.

Filipic, M.; Zegura, B.; Sedmak, B.; Horvat-Znidarsic, I.; Milutinovic, A.; Suput, D. Subchronic exposure of rats to sublethal dose of microcystin-YR induces DNA damage in multiple organs. Radiology and Oncology, v. 41, p. 15-22, 2007.

Gatta, A.; Bazzerla, G.; Amodio, P.; Menon, F.; Angeli, P.; Schiaffino, E.; Schmicd, C. Detection of the early steps of cadmium nephropathy: Comparison of light and electron-microscopical patterns with the urinary enzymes excretion. Nephron, v. 51, p. 20-24, 1989.

Ghasemi, K.; Ghasemi, Y.; Ebrahimzadeh, M. A. Antioxidant activity, phenol and flavonoid contents of 13 citrus species peels and tissues. Pakistan Journal of Pharmaceutical Sciences, v. 22, p. 277-281, 2009.

Gil-Izquierdo, A.; Gil, M.I.; Ferreres, F.; Tomas-Barberan, F. A. In vitro availability of flavonoids and other phenolics in orange juice. Journal of Agricultural and Food Chemistry, v. 49, p. 1035-1041, 2001.

Giri, J.; Sathidevi, T.; Dushyanth, N. Effects of jamun seed extract on alloxan induced diabetes in rats. Journal of the Diabetic Association of India, v. 25, p. 115-119, 1985.

Gorinstein, S.; Martin-Belloso, O.; Park, Y.; Haruenkit, R.; Ciz, M. Comparison of some biochemical characteristics of different citrus fruits. Food Chemistry, v. 74, p. 309-315, 2001.

Greer, B.; Meneely, J. P.; Elliott, C. T. Uptake and accumulation of Microcystin-LR based on exposure through drinking water: An animal model assessing the human health risk. Scientific Reports, v. 8, 4913, 2018. https://doi.org/10.1038/s41598-018-23312-7

Hegazy, A. E.; Ibrahim, M. I. Antioxidant activities of orange peel extract. World Applied Sciences Journal, v. 18, p. 684-688, 2012. https://doi.org/10.5829/idosi.wasj.2012.18.05.64179

Hooser, S. B.; Beasley, V. R.; Basgall, E. J.; Carmichael, W. W.; Haschek, W. M. Microcystin-LR-induced ultrastructural changes in rats. Veterinary Pathology, v. 27, p. 9-15, 1990. https://doi.org/10.1177/030098589002700102

Hooser, S. B.; Beasley, V. R.; Lovell, R. A.; Carmichael, W. W.; Haschek, W. M. Toxicity of microcystin-LR, a cyclic hepatopeptide hepatotoxin from Microcystis aeruginosa to rats and mice. Veterinary Pathology, v. 26, p. 246-252, 1989. https://doi.org/10.1177/030098588902600309

Jadhav, S. H.; Sarkar, S. N.; Patil, R. D.; Tripathi, H. C. Effects of subchronic exposure via drinking water to a mixture of eight water-contaminating metals: A biochemical and histopathological study in male rats. Archives of Environmental Contamination and Toxicology, v. 53, p. 667-677, 2007. https://doi.org/10.1007/s00244-007-0031-0

Jihen, H.; Imed, M.; Fatima, H.; Abdelhamid, K. Protective effects of selenium (Se) and zinc (Zn) on cadmium (Cd) toxicity in the liver and kidney of the rat: Histology and Cd accumulation. Food and Chemical Toxicology, v. 46, p. 3522-3527, 2008. https://doi.org/10.1016/j.fct.2008.08.037

Karmakar, N.; Saxena, R.; Anad, R. Histopathological changes in rat tissues by oral intake of lead acetate. Environmental Research, v. 41, p. 23-28, 1986.

Kerem, M.; Bedirli, N.; Gurbuz, N.; Ekinci, O.; Akkaya, T.; Sakrak, O.; Pasaoglu, H. Effects of acute fenthion toxicity on liver and kidney function and histology in rats. Turkish Journal of Medical Sciiences, v. 37, p. 281-288, 2007.

Khan, S.; Kumari, D. Analytical study of histopathological changes induced by endosulfane in kidney of Albino rat. Asian Jornal of Pharmaceutical and Clinical Research, v. 5, p. 113-114, 2012. https://doi.org/10.22270/jddt.v4i3.837

Kim, B.; Cho, J. W.; Kwon, H. N.; Blank, I.; Borisova, I.; Ejaz, S.; Chekarova, I.; Kwon, J.; Lim, C. W. Hepatotoxicity induced by microcystin-LR in rat. Journal of Toxicology and Public Health, v. 22, p. 375-380, 2006.

Korkmaz, N.; Cengiz, E. I.; Unlu, E.; Uysal, E.; Yanar, M. Cypermethrin-induced histopathological and biochemical changes in Nile tilapia (Oreochromis niloticus), and the protective and recuperative effect of ascorbic acid. Environmental Toxicology and Pharmacology, v. 28, p. 198-205, 2009. https://doi.org/10.1016/j.etap.2009.04.004

Kotak, B. J.; Semalulu, S.; Friytz, D. L.; Prepas, E. E.; Hrudey, S. E.; Coppock, R. W. Hepatic and renal pathology of intraperitoneally administered microcystin-LR in rainbow trout (Oncorhynchus mykiss). Toxicon, v. 34, p. 517-525, 1996.

Kukner, A.; Colakoglu, N.; Kara, H.; Oner, H.; Ozogul, C.; Ozan, E. Ultrastructural changes in the kidney of rats with acute exposure to cadmium and effects of exogenous metallothionein. Biological Trace Element Research, v. 119, p. 137-146, 2007. https://doi.org/10.1007/s12011-007-0049-1

Kuru, M.; Ugras, M.; Esrefoglu, M. Effect of resveratrol on tubular damage and interstitial fibrosis in kidneys of rats exposed to cigarette smoke. Toxicology and Industrial Health, v. 25, p. 539-544, 2009. https://doi.org/10.1177/0748233709346755

Lamfon, H. A.; Al-Rawi, M. M. Effect of antox and paraquat-induced histological and biochemical changes in kidney of albino rats. Journal of Applied Sciences Research, v. 3, p. 988-993, 2007.

Madhuri, S.; Ashwini, U.H.; Srilakshmi, N. S.; Prashith, K. R. Antimicrobial activity of Citrus sinensis and Citrus aurantium peel extracts. Journal of Pharmaceutical and Scientific Innovation, v. 3, p. 366-368, 2014.

Muhtadi, H.; Azizah, T.; Suhendi, A.; Yen, K. H. Antidiabetic and antihypercholesterolemic activities of Citrus sinensis peel: In vivo study. National Journal of Physiology Pharmacy and Pharmacology, v. 5, p. 382-385, 2015. https://doi.org/10.5455/njppp.2015.5.2807201561

Muthuviveganandavel, V.; Muthuraman, P.; Muthu, S.; Srikumar, K. A study on low dose cypermethrin induced histopathology, lipid peroxidation and marker enzyme changes in male rat. Pesticide Biochemistry and Physiology, v. 91, p. 12-16, 2008. https://doi.org/10.1016/j.pestbp.2007.11.010

Negri, A. P.; Jones, G. J.; Hindmarsh, M. Sheep mortality associated with paralytic shellfish poisoning toxins from the cyanobacterium Anabaena circinalis. Toxicon, v. 33, p. 1321-1329, 1995.

Nunes, J.; Ehrich, M.; Robertson, J. Toxicosis associated with dual oral exposure of rats to lead and trichloroethylene. Toxicologic Pathology, v. 29, p. 451-457, 2001.

Papadimitriou, T.; Kagalou, I.; Stalikas, C.; Pilidis, G.; Leonardos, I. D. Assessment of microcystin distribution and biomagnification in tissues of aquatic food web compartments from a shallow lake and evaluation of potential risks to public health. Ecotoxicology, v. 21, p. 1155-1166, 2012. https://doi.org/10.1007/s10646-012-0870-y

Parashar, S.; Sharma, H.; Garg, M. Antimicrobial and antioxidant activities of fruits and vegetable peels: A review. Journal of Pharmacognosy and Phytochemistry, v. 3, p. 160-164, 2014.

Prakash, C.; Kumar, A.; Prasad, M.; Srivastav, S. K.; Srivastav, A. K. Microcystin-LR attenuates blood calcium and phosphate levels in stinging catfish Heteropneustes fossilis. International Journal of Pharma and Bio Sciences, v. 6, p. 1147-1153, 2015.

Prepas, E. E.; Kotak, B. G.; Campell, L. M.; Evans, J. C.; Hrudey, S. E. Accumulation and elimination of cyanobacterial hepatoxins by the freshwater clam Anodonta grandissimponiana. Canadian Journal of Fisheries and Aquatic Sciences, v. 54, p. 41-46, 1997.

Rabergh, C. M. I.; Bylund, G.; Eriksson, J. E. Histopathological effects of microcystin-LR, acyclic peptide toxin from the cyanobacterium (blue-green alga) Microcystis aeruginosa, on common carp (Cyprinus carpio L.). Aquatic Toxicology, v. 20, p. 131-145, 1991.

Ramful, D.; Bahorum, T.; Bourdom, E.; Tarmus, E.; Aruoma, O. I. Bioactive phenolics and antioxidant propensity of flavedo extracts of Mauritian citrus fruits: Potential prophylactic ingredients for functional foods application. Toxicology, v. 278, p. 75-87, 2010. https://doi.org/10.1016/j.tox.2010.01.012

Rangel, M.; Martins, J. C. G.; Garcia, A. N.; Conserva, A. A.; Costa-Neves, A.; Anna, C. L. S.; Carvalho, L. R. Analysis of the toxicity and histopathology induced by the oral administration of Pseudanabaena galatea and Geitlerinema splendidum (Cyanobacteria) extracts to mice. Marine Drugs, v. 12, p. 508-524, 2014. https://doi.org/10.3390/md12010508

Raza, A.; Butt, M. S.; Ul-Haq, I.; Suleria, H. A. R. Jamun (Syzygium cumini) seed and fruit extract attenuate hyperglycemia in diabetic rats. Asian Pacific Journal of Tropical Biomedicine, v. 7, p. 750-754, 2017. https://doi.org/10.1016/j.apjtb.2017.07.006

Sanchez-Chardi, A.; Penarroja-Matutano, C.; Borras, M.; Nadal, J. Bioaccumulation of metals and effects of a landfill in small mammals. Part III: Structural alterations. Environmental Research, v. 109, p. 960-967, 2009. https://doi.org/10.1016/j.envres.2009.08.004

Shahi, N.; Monalisa, S.; Mallika, S. K.; Sarmaa, D.; Dasa, P. The microcystins-induced DNA damage in the liver and the heart of zebrafish, Danio rerio. Toxicological and Environmental Chemistry, v. 94, p. 340-349, 2012.

Shashi, A.; Singh, J. P.; Thapar, S. P. Toxic effects of fluoride on rabbit kidney. Fluoride, v. 35, p. 38-50, 2002.

Srivastava, B. D.; Srivastav, A. K. Hepatoprotective effects of extracts of Syzygium cumini seeds and Citrus sinensis peels against microcystin LR-induced toxicity in rat. International Journal of Zoological Investigations, v. 3, p. 95-105, 2017.

Srivastava, B. D.; Srivastava, M.; Srivastav, S. K.; Suzuki, N.; Srivastav, A. K. Cypermethrin-induced liver histopathology in rat: Protective role of jamun seed and orange peel extracts. Iranian Journal of Toxicology, v. 12, p. 25-30, 2018.

Srivastava, S. K.; Tiwari, P. R.; Srivastav, A. K. Effects of chlorpyrifos on the kidney of freshwater catfish, Heteropneustes fossilis. Bulletin of Environmental Contamination and Toxicology, v. 45, p. 748-751, 1990.

Suput, D. Effects of microcystins, cyanobacterial toxins, on mammalian cells and organs. Acta Chimica Slovenica, v. 58, p. 708-716, 2011.

Swami, S. B.; Thakor, N. S. J.; Patil, M. M.; Haldankar, P. M. Jamun (Syzygium cumini (L.)): A review of its food and medicinal uses. Food and Nutrition Sciences, v. 3, p. 1100-1117, 2012.

Thijssen, S.; Maringwa, J.; Faes, C.; Lambricht, I.; Van Kerkhove, E. Chronic exposure of mice to environmentally relevant, low doses of cadmium leads to early renal damage, not protected by blood or urine cadmium levels. Toxicology, v. 229, p. 145-156, 2007. https://doi.org/10.4236/fns.2012.38146

Tripathi, S.; Srivastav, A. K. Cytoarchitectural alterations in kidney of Wistar rat after oral exposure to cadmium chloride. Tissue and Cell, v. 43, p. 131-136, 2011. https://doi.org/10.1016/j.tice.2011.01.001

Tripathi, S.; Srivastav, A. K. Nephrotoxicity induced by long-term oral administration of different doses of chlorpyrifos. Toxicology and Industrial Health, v. 26, p. 439-447, 2010. https://doi.org/10.1177/0748233710371110

Velisek, J.; Svobodova, Z.; Piackova, V. Effects of acute exposure to bifenthrin on some haematological, biochemical and histopathological parameters of rainbow trout (Oncorhynchus mykiss). Veterinarni Medicina, v. 54, p. 131-137, 2009. https://doi.org/10.17221/15/2009-VETMED

Wang, Z.; Li, G.; Wu, Q.; Liu, C.; Shen, J.; Yan, W. Microcystin-LR exposure induced nephrotoxicity by triggering apoptosis in female zebrafish. Chemosphere, v. 214, p. 598-605, 2019. https://doi.org/10.1016/j.chemosphere.2018.09.103

Wangsongsak, A.; Utarnpongsa, S.; Kruatrachue, M.; Ponglikitmongkol, M.; Pokethitiyook, P.; Sumranwanich, T. Alterations of organ histopathology and metallothionein mRNA expression in liver barb, Puntius gonionotus during subchronic cadmium exposure. Journal of Environmental Sciences, v. 19, p. 1341-1348, 2007. https://doi.org/10.1016/S1001-0742(07)60219-8

Watanabe, M. F.; Harada, K. I.; Carichael, W. W.; Fujiki, H. Toxic microcystis. Boca Raton: CRC Press, 1996.

Williams, D. E.; Dawe, S. C.; Kent, M. L.; Andersen, R. J.; Craig, M. Bioaccumulation and clearance of microcystins from salt water mussels, Mytilus edulis, and in vivo evidence for covalently bound microcystins in mussel tissues. Toxicon, v. 35, p. 1617-1625, 1997.

Xie, L.; Xie, P.; Guo, L.; Miyabara, Y.; Park, H. Organ distribution and bioaccumulation of microcystins in freshwater fish and different trophic levels from the eutrophic Lake Chaohu, China. Environmental Toxicology, v. 20, p. 293-300, 2005.

Xiping, Y.; Shuaishuai, X.; Feiyu, H.; Cong, W.; Shuilin, Z.; Hai, F.; Jian, G.; Jihua, C.; Xiangling, F.; Fei, Y. Effects of chronic exposure to microcystin-LR on kidney in mice. International Journal of Environmental Research and Public Health, v. 16, no. 24, 5030, 2019. https://doi.org/10.3390/ijerph16245030

Zhang, D.; Den, X.; Xie, P.; Yang, Q.; Chen, J.; Dai, M. Determination of microcystin-LR and its metabolites in snail (Bellamya aeruginosa), shrimp (Macrobrachium nipponensis) and silver carp (Hypophthalmichthys molitrix) from Lake Taihu, china. Chemosphere, v. 76, p. 974-981, 2009. https://doi.org/10.1016/j.chemosphere.2009.04.034

Zhao, S.; Liu, Y.; Wang, F.; Xu, D.; Xie, P. N-acetylcysteine protects against microcystin-LR-induced endoplasmic reticulum stress and germ cell apoptosis in zebrafish testes. Chemosphere, v. 204, p. 463-473, 2018. https://doi.org/10.1016/j.chemosphere.2018.04.020

Zin, L. L.; Edwards, W. C. Toxicity of blue-green algae in livestock. Bovine Practioner, v. 14, p. 151-153, 1979.


ISSN 2358-2731