HISTOMORPHOLOGICAL AND BIOCHEMICAL EFFECT OF METHAMPHETAMINE (CRYSTAL ICE) ON THE HEART OF WISTAR RATS
Main Article Content
Keywords
Methamphetamine, Crystal ice, Cardiotoxicity, Histomorphology, Wistar rats, Biochemical markers
Abstract
Background: Methamphetamine (METH), commonly known as crystal ice, is a potent psychostimulant associated with oxidative stress–mediated organ toxicity. While its neurotoxic effects are well established, its structural and biochemical impact on the heart remains comparatively underexplored. METH induces excessive production of reactive oxygen species, contributing to cellular injury and tissue degeneration. This study evaluated the histomorphological and biochemical effects of graded doses of METH on the hearts of Wistar rats.
Methods: Adult Wistar rats were divided into five groups: a control group and four experimental groups administered 0.5 mg/kg, 1.0 mg/kg, 3.0 mg/kg, and 5.0 mg/kg of METH, respectively, for six weeks. Blood samples were analyzed for haematological and biochemical parameters, and cardiac tissues were processed for histopathological examination. Data were expressed as mean ± SD and analyzed using ANOVA with Scheffé post hoc testing. Statistical significance was set at p < 0.05.
Results: METH administration produced a significant reduction in body weight compared with control (202.7 ± 3.11 g vs 210.0 ± 5.30 g; t = 5.987; p = 0.0001). Haematological analysis showed significant decreases in haematocrit (41.0 ± 1.66 vs 45.6 ± 1.50; t = 20.917; p = 0.0001) and white blood cell count (2.3 ± 0.55 vs 7.4 ± 1.92; t = 9.039; p = 0.004), with a significant increase in monocyte count (17.2 ± 2.38 vs 7.4 ± 1.14; t = −8.684; p = 0.0001). Serum biochemical parameters demonstrated dose-dependent increases in AST (123.1 ± 3.85 to 140.2 ± 0.72 U/L), ALT (62.5 ± 2.48 to 82.0 ± 1.96 U/L), ALP (210.5 ± 6.81 to 241.2 ± 7.15 U/L), and total bilirubin (0.56 ± 0.08 to 0.75 ± 0.05 mg/dL), all statistically significant (p < 0.05). Histological examination revealed normal myocardial architecture in control and 0.5 mg/kg groups, whereas 1.0 mg/kg and 3.0 mg/kg groups exhibited myocyte fragmentation and karyolysis consistent with myolysis.
Conclusion: Chronic methamphetamine exposure induces significant biochemical alterations and histomorphological evidence of myocardial degeneration in Wistar rats, demonstrating its cardiotoxic potential.
References
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24.Ezeukwu AO, Egwuonwu AV, John JN, Ekediegwu E, Mgbeojedo UG, Ekechukwu EN. Assessment of Adiposity Indices among Female Staff in University of Nigeria Primary School Enugu Campus. African Journal of Health Sciences and Technology 1 (2), 37-45
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29.Esmaeilpour T, Lotfealian A, Anvari M, Namavar M, Karbalaei N, Shahedi A, Bokkon I, Salari V, Oblak D. Effect of methamphetamine on ultraweak photon emission and level of reactive oxygen species in male rat brain. Neuroscience Letters. 2023 Mar 28;801:137136.
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32.Hothorn LA. Tests for strict monotonic trend in bio-medical dose-response relationships (respective concentration-response or exposure-response relationships)--a biostatistical perspective. arXiv preprint arXiv:2311.01480. 2023 Nov 2.
33.Han JH, Kwak JY, Lee SS, Kim HG, Jeon H, Cha RR. Markedly elevated aspartate aminotransferase from non-hepatic causes. Journal of clinical medicine. 2022 Dec 30;12(1):310.
34.Karatas M, Keles N, Parsova KE, Ciftci HO, Ozkok S, Kahraman E, Durak F, Kocogullari CU, Yiyit N. High AST/ALT ratio is associated with cardiac involvement in acute COVID-19 patients. Medicina. 2023 Jun 16;59(6):1163.
35.Perrone S, Lembo C, Giordano M, Petrolini C, Cannavò L, Gitto E. Molecular mechanisms of oxidative stress‐related neonatal jaundice. Journal of biochemical and molecular toxicology. 2023 Jun;37(6):e23349.
36.Pires B, Rosendo LM, Brinca AT, Simão AY, Barroso M, Rosado T, Gallardo E. The therapeutic potential of amphetamine-like psychostimulants. Life. 2023 Nov 8;13(11):2180.
37.Martinez-Sanchez N, Sweeney O, Sidarta-Oliveira D, Caron A, Stanley SA, Domingos AI. The sympathetic nervous system in the 21st century: Neuroimmune interactions in metabolic homeostasis and obesity. Neuron. 2022 Nov 2;110(21):3597-626.
38.Thakkar AB, Durstenfeld MS, Ma Y, Win S, Hsue PY. Methamphetamine-associated heart failure: Clinical characteristics and outcomes in a safety net population. Heart & Lung. 2025 Mar 1;70:214-22.
39.To M, Savoj J, Kraft J, Chang J, Ayutyanont N, Vandeveer C, Gulati R, Biswas M, Vandever C, Biswas MS. Assessment of Contributing Risk Factors Leading to Heart Failure in Patients Who Are Methamphetamine Users. Cureus. 2024 Dec 27;16(12).
40.Ellis JD, Rabinowitz JA, Ware OD, Wells J, Dunn KE, Huhn AS. Patterns of polysubstance use and clinical comorbidity among persons seeking substance use treatment: An observational study. Journal of substance use and addiction treatment. 2023 Mar 1;146:208932.
41.Stiltner B, Pietrzak RH, Tylee DS, Nunez YZ, Adhikari K, Kranzler HR, Gelernter J, Polimanti R. Polysubstance addiction patterns among 7,989 individuals with cocaine use disorder. Iscience. 2023 Aug 18;26(8).
42.Rockhill KM, Black JC, Iwanicki J, Abraham A. Polysubstance use profiles among the general adult population, United States, 2022. American Journal of Public Health. 2025 May;115(5):747-57.
43.Stojiljković MP, Lončar-Stojiljković D, Marinković ST, Bojić M, Škrbić R. Cardiovascular Toxicity of Catecholamines. InCardiovascular Toxicity: Incidence, Pathogenesis and Treatment Strategies 2025 Oct 1 (pp. 111-130). Cham: Springer Nature Switzerland.
44.Owolabi MO, Platz T, Good D, Dobkin BH, Ekechukwu EN, Li L. Translating innovations in stroke rehabilitation to improve recovery and quality of life across the globe. Frontiers in Neurology. 2020 Dec 14;11:630830.
45.Ekechukwu EN, Okaku MO, Adaramola S, Onuorah IN. Patterns and predictors of work-related musculoskeletal disorders among commercial tricycle (keke napep) riders in Nigeria. InCongress of the International Ergonomics Association 2018 Aug 5 (pp. 765-777). Cham: Springer International Publishing.
2.Gu C, Geng YC, Zhu LN. Dysregulation of dopamine neurotransmission in drug addicts: implications for criminal behavior and corrective interventions. Frontiers in psychiatry. 2024 Nov 25;15:1434083.
3.Omidvari S, Azimzadeh Z, Rashnoo F, Tahmasebinia F, Keramatinia A, Roozbahany NA, Abbaszadeh HA, Darabi S. Molecular mechanisms and treatment strategies for methamphetamine induced neurodegeneration, inflammation and neurotoxicity. Acta neurobiologiae experimentalis. 2023 Dec 28;83(4):414-31.
4.Rashidi SK, Khodagholi F, Rafie S, Kashipazha D, Safarian H, Khoshnam SE, Dezfouli MA. Methamphetamine and the brain: Emerging molecular targets and signaling pathways involved in neurotoxicity. Toxin Reviews. 2024 Oct 1;43(4):553-71.
5.Anyanwu GE, Umeano AV, Ojiakor VO, Katchy AU, Anyanwu CN, Fakorede S. Morin Mitigates Methamphetamine-Induced Neurotoxicity: Effects on Motor and Cognitive Function. Journal of Experimental Pharmacology. 2025 Dec 31:307-21.
6.Kolluru GK, Glawe JD, Pardue S, Kasabali A, Alam S, Rajendran S, Cannon AL, Abdullah CS, Traylor JG, Shackelford RE, Woolard MD. Methamphetamine causes cardiovascular dysfunction via cystathionine gamma lyase and hydrogen sulfide depletion. Redox biology. 2022 Nov 1;57:102480.
7.Annawald K, Streckfuss-Bömeke K, Meyer T. Methamphetamine-induced cardiotoxicity: in search of protective transcriptional mechanisms. Herz. 2024 Dec;49(6):434-40.
8.Ramli FF, Rejeki PS, Abdullayeva G, Halim S. A mechanistic review on toxicity effects of methamphetamine. International journal of medical sciences. 2025 Jan 1;22(3):482.
9.Krogh LC. Practice Considerations for the Methamphetamine Use Disorder Patient. Nursing Clinics. 2023 Jun 1;58(2):227-41..
10.Safdari KM, Converse C, Dong F, MacDougall NA, Hyer K, Runyon A, Ahlering H, Comunale ME. Hemodynamic effects of methamphetamine and general anesthesia. Anesthesiology Research and Practice. 2022;2022(1):7542311.
11.Manja V, Nrusimha A, Gao Y, Sheikh A, McGovern M, Heidenreich PA, Sandhu AT, Asch S. Methamphetamine-associated heart failure: a systematic review of observational studies. Heart. 2023 Feb 1;109(3):168-77.
12.Hemphill K, Tierney S, Tirschwell D, Davis AP. A review of methamphetamine use and stroke in the young. Frontiers in neurology. 2024 Apr 24;15:1397677.
13.Granado N, Mendieta L, Tizabi Y, Murer MG, Moratalla R. Attenuated neurotoxicity after repeated methamphetamine binges linked to dopamine transporter (DAT) decline. Neurobiology of Disease. 2025 Apr 1;207:106839.
14.Tobolski J, Sawyer DB, Song SJ, Afari ME. Cardiovascular disease associated with methamphetamine use: a review. Heart failure reviews. 2022 Nov;27(6):2059-65.
15.Zarei F, Simani M, Moghaddam HR, Ghaderi A. A review of cardiovascular diseases in substance use disorders: current knowledge and future perspectives. Addiction & Health. 2025 Dec 20;17:1722.
16.Chen L, Ru Q, Xiong Q, Yang J, Xu G, Wu Y. Potential effects of Nrf2 in exercise intervention of neurotoxicity caused by methamphetamine oxidative stress. Oxidative medicine and cellular longevity. 2022;2022(1):4445734.
17.Wang B, Wang Y, Zhang J, Hu C, Jiang J, Li Y, Peng Z. ROS-induced lipid peroxidation modulates cell death outcome: mechanisms behind apoptosis, autophagy, and ferroptosis. Archives of toxicology. 2023 Jun;97(6):1439-51.
18.Endale HT, Tesfaye W, Mengstie TA. ROS induced lipid peroxidation and their role in ferroptosis. Frontiers in cell and Developmental Biology. 2023 Aug 1;11:1226044.
19.Edinoff AN, Kaufman SE, Green KM, Provenzano DA, Lawson J, Cornett EM, Murnane KS, Kaye AM, Kaye AD. Methamphetamine use: a narrative review of adverse effects and related toxicities. Health Psychology Research. 2022 Sep 15;10(3):38161.
20.Pang L, Wang Y. Overview of blood-brain barrier dysfunction in methamphetamine abuse. Biomedicine & Pharmacotherapy. 2023 May 1;161:114478.
21.Ekechukwu NE, Okoh AC. Effects of six weeks donkey kick and squat resistance exercises on gluteal adiposity, muscle strength, and muscle bulk of young Nigerian female adults: a randomized controlled trial. International Journal of Medicine and Health Development. 2020 Jan 1;25(1):28-37.
22.Lindsey ML, Brunt KR, Kirk JA, Kleinbongard P, Calvert JW, de Castro Brás LE, DeLeon-Pennell KY, Del Re DP, Frangogiannis NG, Frantz S, Gumina RJ. Guidelines for in vivo mouse models of myocardial infarction. American Journal of Physiology-Heart and Circulatory Physiology. 2021 Dec 1;321(6):H1056-73.
23.Okonkwo UP, Ibeneme SC, Ihegihu C, Ezema IC, Okoye EC, Egwuonwu VA, Ekechukwu EN, Azubike O. Stroke Severity Variations in a 12 Month Prospective Study Involving Sub-acute Ischemic Stroke Survivors With and Without Cognitive Impairment in Nnewi, Nigeria. Asian Journal of Research and Reports in Neurology. 2018 Jul 18;1(1):6-17.
24.Ezeukwu AO, Egwuonwu AV, John JN, Ekediegwu E, Mgbeojedo UG, Ekechukwu EN. Assessment of Adiposity Indices among Female Staff in University of Nigeria Primary School Enugu Campus. African Journal of Health Sciences and Technology 1 (2), 37-45
25.Ekechukwu EN, Chimereze NR, Atueyi BB, Ekediegwu E. Sociodemographic and Clinical Characteristics of Children with Erb’s Palsy and the Clinical Specialization of Their Therapists-A Retrospective Study. African Journal of Health Sciences, 2021 December; 3(2):. 176-186
26.Henn D. In Vitro Cytotoxic and Ultrastructural Effects of Selected Carboxylic Ionophores on Cardiac and Skeletal Myoblasts (Doctoral dissertation, University of Pretoria (South Africa).
27.Stirbu CM, Vasiliniuc AC, Vasiliu A, Liehn EA. Heartbreakers: Decoding the Molecular Dynamics of Stimulants Abuse on the Cardiovascular System. Discoveries. 2025 May 10;13(2):e207.
28.Abood MT, Mohammed MT. Methamphetamine-Induced Oxidative Stress and Inflammatory Markers as Indicators of Blood-Brain Barrier Disruption. Reports of Biochemistry & Molecular Biology. 2025 Jul 1;14(2).
29.Esmaeilpour T, Lotfealian A, Anvari M, Namavar M, Karbalaei N, Shahedi A, Bokkon I, Salari V, Oblak D. Effect of methamphetamine on ultraweak photon emission and level of reactive oxygen species in male rat brain. Neuroscience Letters. 2023 Mar 28;801:137136.
30.Esmaeilpour T, Lotfealian A, Anvari M, Namavar M, Karbalaei N, Shahedi A, Bokkon I, Salari V, Oblak D. Effect of methamphetamine on ultraweak photon emission and level of reactive oxygen species in male rat brain. Neuroscience Letters. 2023 Mar 28;801:137136. Davis JM, Svendsgaard DJ. Nonmonotonic dose-response relationships in toxicological studies. InBiological Effects of Low Level Exposures Dose-Response Relationships 2024 Nov 1 (pp. 67-85). CRC Press.
31.van der Most MA, Rietjens IM, van den Brink NW. Evaluating non-monotonic dose-response relationships in ecotoxicological risk assessment: A case study based on a systematic review of data on fluoxetine. Chemosphere. 2024 Sep;363(April):142819.
32.Hothorn LA. Tests for strict monotonic trend in bio-medical dose-response relationships (respective concentration-response or exposure-response relationships)--a biostatistical perspective. arXiv preprint arXiv:2311.01480. 2023 Nov 2.
33.Han JH, Kwak JY, Lee SS, Kim HG, Jeon H, Cha RR. Markedly elevated aspartate aminotransferase from non-hepatic causes. Journal of clinical medicine. 2022 Dec 30;12(1):310.
34.Karatas M, Keles N, Parsova KE, Ciftci HO, Ozkok S, Kahraman E, Durak F, Kocogullari CU, Yiyit N. High AST/ALT ratio is associated with cardiac involvement in acute COVID-19 patients. Medicina. 2023 Jun 16;59(6):1163.
35.Perrone S, Lembo C, Giordano M, Petrolini C, Cannavò L, Gitto E. Molecular mechanisms of oxidative stress‐related neonatal jaundice. Journal of biochemical and molecular toxicology. 2023 Jun;37(6):e23349.
36.Pires B, Rosendo LM, Brinca AT, Simão AY, Barroso M, Rosado T, Gallardo E. The therapeutic potential of amphetamine-like psychostimulants. Life. 2023 Nov 8;13(11):2180.
37.Martinez-Sanchez N, Sweeney O, Sidarta-Oliveira D, Caron A, Stanley SA, Domingos AI. The sympathetic nervous system in the 21st century: Neuroimmune interactions in metabolic homeostasis and obesity. Neuron. 2022 Nov 2;110(21):3597-626.
38.Thakkar AB, Durstenfeld MS, Ma Y, Win S, Hsue PY. Methamphetamine-associated heart failure: Clinical characteristics and outcomes in a safety net population. Heart & Lung. 2025 Mar 1;70:214-22.
39.To M, Savoj J, Kraft J, Chang J, Ayutyanont N, Vandeveer C, Gulati R, Biswas M, Vandever C, Biswas MS. Assessment of Contributing Risk Factors Leading to Heart Failure in Patients Who Are Methamphetamine Users. Cureus. 2024 Dec 27;16(12).
40.Ellis JD, Rabinowitz JA, Ware OD, Wells J, Dunn KE, Huhn AS. Patterns of polysubstance use and clinical comorbidity among persons seeking substance use treatment: An observational study. Journal of substance use and addiction treatment. 2023 Mar 1;146:208932.
41.Stiltner B, Pietrzak RH, Tylee DS, Nunez YZ, Adhikari K, Kranzler HR, Gelernter J, Polimanti R. Polysubstance addiction patterns among 7,989 individuals with cocaine use disorder. Iscience. 2023 Aug 18;26(8).
42.Rockhill KM, Black JC, Iwanicki J, Abraham A. Polysubstance use profiles among the general adult population, United States, 2022. American Journal of Public Health. 2025 May;115(5):747-57.
43.Stojiljković MP, Lončar-Stojiljković D, Marinković ST, Bojić M, Škrbić R. Cardiovascular Toxicity of Catecholamines. InCardiovascular Toxicity: Incidence, Pathogenesis and Treatment Strategies 2025 Oct 1 (pp. 111-130). Cham: Springer Nature Switzerland.
44.Owolabi MO, Platz T, Good D, Dobkin BH, Ekechukwu EN, Li L. Translating innovations in stroke rehabilitation to improve recovery and quality of life across the globe. Frontiers in Neurology. 2020 Dec 14;11:630830.
45.Ekechukwu EN, Okaku MO, Adaramola S, Onuorah IN. Patterns and predictors of work-related musculoskeletal disorders among commercial tricycle (keke napep) riders in Nigeria. InCongress of the International Ergonomics Association 2018 Aug 5 (pp. 765-777). Cham: Springer International Publishing.
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Nov 04, 2026
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Ngozika O. Achukwu, Paschal Maduka, Anulika O. Onyemelukwe, Cornelius OGU, Echezona N.D. Ekechukwu, & Peter U. Achukwu. (2026). HISTOMORPHOLOGICAL AND BIOCHEMICAL EFFECT OF METHAMPHETAMINE (CRYSTAL ICE) ON THE HEART OF WISTAR RATS. Journal of Population Therapeutics and Clinical Pharmacology, 33(3), 01-13. https://doi.org/10.67145/wn06m682
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How to Cite
Ngozika O. Achukwu, Paschal Maduka, Anulika O. Onyemelukwe, Cornelius OGU, Echezona N.D. Ekechukwu, & Peter U. Achukwu. (2026). HISTOMORPHOLOGICAL AND BIOCHEMICAL EFFECT OF METHAMPHETAMINE (CRYSTAL ICE) ON THE HEART OF WISTAR RATS. Journal of Population Therapeutics and Clinical Pharmacology, 33(3), 01-13. https://doi.org/10.67145/wn06m682
