Research on antemortem condition elucidation of methamphetamine detected forensic autopsy cases : investigation of trouble of skeletal muscle and kidney

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15390215
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Legal medicine
• Research Institution: The University of Tokushima
• Principal Investigator: KUBO Shin-ichi The Univ.of Tokushima, Institute of Health Biosciences, Professor, 大学院・ヘルスバイオサイエンス研究部, 教授 (10205122)
• Co-Investigator(Kenkyū-buntansha): TOKUNAGA Itsuo The Univ.of Tokushima, Institute of Health Biosciences, Associate Professor, 大学院・ヘルスバイオサイエンス研究部, 助教授 (30116842) ; KITAMURA Osamu The Univ.of Tokushima, Institute of Health Biosciences, Lecturer, 大学院・ヘルスバイオサイエンス研究部, 講師 (70266609) ; GOTOHDA Takako The Univ.of Tokushima, Institute of Health Biosciences, Assistant, 大学院・ヘルスバイオサイエンス研究部, 助手 (50304506) ; ISHIGAMI Akiko Tokushima Prefectural Police Headquarters, Assistant Part-time doctor, 非常勤医師
• Project Period (FY): 2003 – 2004
• Keywords: methamphetamine / cause of death / renal function / skeletal muscle damage / myoglobin / oxidative damage / peroxidative DNA injury / immunohistochemistry

Research Abstract

In 2003, we had an immunhistochemical study on the kidney of 22 forensic autopsy cases in which methamphetamine (MA) had been detected. Myoglobin was positive in 72.7% of them. It was suspected that MA had damaged skeletal muscle. Eighty percent of HSP70-positive cases were myoglobin-positive. Myoglobin was also observed in 60.0% of 8-OH-dG-positive, in 88.6% of 4-HNE-positive, and in 77.8% of SOD-positive cases, respectively. Therefore, it was suspected that myoglobin induced oxidative injury. The relation between immunoreactivity of these substances and the concentration of MA was not found statistically. This study suggests that immunhistochemical staining of myoglobin, HSP70, 8-OH-dG, 4-HNE, and SOD contributes to presumption of the condition (just) before MA abuser's death. In 2004, we investigated the influence of MA to the kidney in rats. The single administration (group I) and the repeated administration (group II) were designed as the acute model, and the subacute or chronic model. Immunohistochemically several cell damage markers were observed. Then, the renal function markers and minerals in blood were measured. Myoglobin and creatinine phosphokinase (CPK) in blood were also analyzed. In group I, ubiquitin immunoreactivity was enhanced only in the renal tubules. Creatinine rose, and K, Ca, and P had decreased (p<0.01). CPK increased significantly (p<0.01). So, it was suspected that MA might induce the renal dysfunction with some damage in renal tubules. This damage might be related to the leakage of CPK from muscle into the blood. In group II, number of 8-OH-dG positive nucleus was increased in kidney, and quantitatively 8-OH-dG was also increased (p<0.01). It was considered that the oxidative DNA damage in the kidney might be induced by repeat administration. Blood Ca has decreased significantly (p<0.01). It was suspected that some renal dysfunction was occurred in relation to the oxidative DNA damage.