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Experimental Protocol for Detecting Mitochondrial Function in Hepatocytes Exposed to Organochlorine Pesticides
Published on: September 16, 2020
Hepatic mitochondrial and peroxisomal alterations in acutely ill malnourished Malawian children: A postmortem cohort
Catriona M Ling1,2, Tewabu F Sheferaw3, Donna M Denno4,5,6
1Department of Nutritional Sciences, University of Toronto, Toronto, Canada.
Insights
Edematous malnutrition in children is linked to fewer and abnormal liver mitochondria and peroxisomes. Improving liver metabolic function may reduce mortality in severely malnourished children.
Area of Science:
- Pediatric pathology
- Nutritional science
- Cellular biology
Background:
- Malnutrition, particularly in children, significantly impacts organ function and mortality.
- Liver mitochondria and peroxisomes play crucial roles in cellular metabolism.
- Understanding organelle pathology in malnutrition is key to developing effective interventions.
Purpose of the Study:
- To compare liver mitochondrial and peroxisomal histopathology in children with varying nutritional statuses (non-wasted, severely wasted, edematous malnutrition).
- To investigate the ultrastructural changes in liver organelles associated with different forms of childhood malnutrition in Malawi.
Main Methods:
- Minimally Invasive Tissue Sampling (MITS) was used to collect liver tissue from children under five who died during hospitalization.
- Histological assessment included hematoxylin and eosin staining, electron microscopy (EM), and immunofluorescence (IF) for ultrastructural characterization.
- Statistical analysis compared organelle abundance and morphology across nutritional groups.
Main Results:
- Hepatic steatosis was prevalent in all malnutrition groups, especially edematous malnutrition.
- Edematous malnutrition was significantly associated with reduced abundance and abnormal morphology of hepatic mitochondria compared to non-wasted and severely wasted children.
- Peroxisomal abundance was reduced in edematous malnutrition compared to severe wasting, but not non-wasting.
Conclusions:
- Edematous malnutrition is characterized by significant alterations in liver mitochondria and peroxisomes.
- Interventions aimed at enhancing hepatic metabolic function could be vital for improving outcomes and reducing mortality in children with severe malnutrition, particularly those with nutritional edema.
Objectives:
To describe and compare liver mitochondrial and peroxisomal histopathology by nutritional status in children who died following hospitalization for acute illness in Malawi.
Methods:
Liver tissue was collected using Minimally Invasive Tissue Sampling from eleven children under-five years old who died during hospitalization and were either non-wasted (n = 4), severely wasted (n = 4) or had edematous malnutrition (n = 3). Histology was assessed on hematoxylin and eosin stained slides. Mitochondrial and peroxisomal ultrastructural features were characterized using electron microscopy (EM) and immunofluorescence (IF).
Results:
Hepatic steatosis was present in 50 % of non-wasted and severely wasted children and all children with edematous malnutrition. Edematous malnutrition was associated with 56 % and 45 % fewer mitochondria than severe wasting (p < 0.001) and no wasting (p = 0.006), respectively, and abnormal mitochondrial morphology compared to severe wasting (p = 0.002) and no wasting (p = 0.035). Peroxisomal abundance was reduced in edematous malnutrition compared to severe wasting (p = 0.005), but did not differ from no-wasting.
Conclusion:
Edematous malnutrition is associated with reduced abundance and altered morphology of hepatic mitochondria and peroxisomes. Interventions targeting improvements in hepatic metabolic function may be beneficial in improving metabolism and reducing mortality in children with severe malnutrition, particularly in those with nutritional edema.
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