Investigation of the hazardous substance causing crayfish-induced rhabdomyolysis via a mouse model, a hemolysis assay, and a cytotoxicity assay

Chen, Xiaofeng; Lin, Jiang-Wei; Pan, Tzu‐Ming; Cao, Min‐Jie; Shi, Chao-lan; Cai, Qiu-Feng; Liu, Guangming

doi:10.1007/s12562-015-0856-9

Cited by 4 publications

(2 citation statements)

References 20 publications

(23 reference statements)

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“…Studies using a mouse model have found that the hazardous substance from crayfish could cause rhabdomyolysis ( 27 , 28 ). This hazardous substance is specific to certain batches of crayfish.…”

Section: Discussionmentioning

confidence: 99%

Outbreak of Haff Disease along the Yangtze River, Anhui Province, China, 2016

Ma¹,

Wu²,

Qin³

et al. 2020

Emerg. Infect. Dis.

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H aff disease is an unexplained rhabdomyolysis that occurs within 24 hours after consumption of certain types of freshwater or saltwater fish (1,2). It was first reported in 1924 in the vicinity of Königsberg along the Baltic coast near Frisches Haff (1-3). Over the next 9 years, an estimated 1,000 persons were affected by similar outbreaks, occurring seasonally in the summer and autumn in this area (3). Although subsequent outbreaks were identified in several other countries, such as Sweden (4), the former Soviet Union (5), Brazil (6,7), Japan (8), and China (9,10), the etiology has not yet been determined. An unidentified heat-stable toxin similar to cyanotoxins or palytoxin, but primarily myotoxic and not neurotoxic, is thought to be the cause of Haff disease (1); however, evidence supporting this hypothesis has been scant. In July 2016, the number of rhabdomyolysis cases reported to the National Foodborne Disease Surveillance System (NFDSS) in China dramatically increased in Anhui Province compared with previous years. Most of the cases were reported in Wuhu and Ma'anshan, cities in Anhui Province in eastern China. Epidemiologic features were compatible with Haff disease (3,6). Preliminary investigation implicated crayfish as the vector. On August 5, the number of cases surpassed 200, prompting an emergency investigation by the Chinese Field Epidemiology Training Program, together with the Anhui Province Center for Disease Control and Prevention (CDC). The objectives of the investigation were to describe the epidemiologic and clinical characteristics, trace back the implicated vectors, identify possible risk factors, and recommend control measures. Methods Case Definition and Finding We defined a case of rhabdomyolysis as any person with elevation in creatine kinase (CK) value plus clinical manifestations of myalgia or limb weakness (10,11). We defined a Haff disease case as illness in any person with acute onset of rhabdomyolysis after ingestion of freshwater fish or seafood within 24 hours in Anhui Province during June-August 2016. We searched for physician-diagnosed rhabdomyolysis cases from the NFDSS, an internetbased, passive surveillance system for foodborne Outbreak of Haff Disease along the Yangtze River,

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Section: Discussionmentioning

confidence: 99%

Outbreak of Haff Disease along the Yangtze River, Anhui Province, China, 2016

Ma¹,

Wu²,

Qin³

et al. 2020

Emerg. Infect. Dis.

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“…Nevertheless, all tested chemicals were negative or lower than the toxicity thresholds [11]. Chen Xiaofeng et al demonstrated that rhabdomyolysis related toxins from crayfish were not an allergen or palytoxin [39]. Chen Yan et al have conducted chemical analysis from crayfish and the blood and urine samples of two patients during the 2010 Nanjing outbreak of Haff disease, and more than 200 compounds with known relevance to rhabdomyolysis were screened, but unfortunately, no possible toxins were revealed [12].…”

Section: Discussionmentioning

confidence: 99%

Ionophore Toxin Maduramicin Produces Haff Disease-Like Rhabdomyolysis in a Mouse Model

Gao

Song

Zuo

et al. 2020

IJERPH

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Maduramicin is a toxic ionophore antibiotic that is isolated from Streptomyces, frequently occurring in an aquatic environment. To understand the potential role of maduramicin in crayfish consumption related Haff disease, a mouse model was established in this study. Two exposure routes of maduramicin in the abdominal muscle and the hepatopancreas tissue homogenates of crayfish were given intragastrically to mice in different doses for seven days. Action changes, clinical symptoms, feed consumption, body weight, blood biochemistry, and histopathology examination of mice were observed and analyzed. In the natural exposure group, relatively low concentration of maduramicin in crayfish muscle and hepatopancreas had no obvious effects on mental state, body weight, blood biochemical indexes, or histologic appearance. However, in the artificial exposure group, with increasing concentrations, maduramicin in crayfish muscle and hepatopancreas homogenates both induced mental sluggishness and weight loss of mice. Blood biochemical examination showed that 3.5 mg·kg−1 and 7 mg·kg−1 maduramicin in crayfish tissue homogenates significantly increased levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), lactate dehydrogenase (LDH), and creatine kinase (CK). Additionally, histopathological examination showed that multiple organs were damaged by maduramicin, including degeneration of liver cells, shedding of renal epithelial cells, and disturbance and partial lysis of myocardial and skeletal muscle filaments in the mice. In summary, maduramicin may not cause Haff disease through contamination of the aquatic environment under normal conditions. Maduramicin can be used as a potential toxin tool to establish a rhabdomyolysis disease animal model for drug development.

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