Khalaf, M. | bioRxiv Science

bioRxiv2024

Local High-Protein, Plant-Based Ready-to-Use Therapeutic Food Enhances Recovery from Malnutrition in Rats

Infant child malnutrition is a major public health issue. We conducted a preclinical study with young rats to mimic the conditions of child malnutrition (combined wasting and stunting) and evaluate recovery using a novel plant-based ready-to-use-therapeutic food (RUTF) formulation. Three-week old female Sprague Dawley rats were assigned to six treatments groups in a 6-week experiment. The treatments included: 1) control balanced diet (CT), 2) A protein-deficient diet to induce malnutrition (MN), 3) and 4) A control balanced diet followed by either commercial RUTF (CT-PM) or a locally produced plant-based RUTF (CT-ChSMS), and 5) and 6) a protein deficient diet followed by either commercial RUTF (MN-PM) or locally produced plant based RUTF (MN-ChSMS), respectively. In treatments 3-6, rats were initially fed either a control-balanced or protein-deficient diet for 3 weeks, followed by 3 weeks of either the commercial or the locally plant-based RUTF. Results showed that rats in the CT-ChSMS group exhibited growth and weight comparable to CT group, while those in the MN-PM group showed no significant improvement compared to the MN group. Notably, rats in the MN-ChSMS group demonstrated significant catch-up growth, whereas those in the MN-PM group did not. Additionally, consumption of ChSMS and PM RUTFs differed significantly. ChSMS RUTF which contained 14% protein over total energy with better amino-acid composition and a higher Protein Digestibility-Corrected Amino Acid Score (PDCAAS), resulted in significantly greater weight gain and length compared to PM RUTF, which contained 10% protein over total energy. These findings indicate that a locally produced, culturally acceptable and affordable plant-based RUTF formulated with high protein quality and quantity may be effective in treating acute and chronic malnutrition in children.

physiology↗

bioRxiv2024

Endogenously produced hydrogen cyanide serves as a novel mammalian gasotransmitter

Small, gaseous molecules, known as gasotransmitters (NO, CO, H2S), are produced endogenously in mammalian cells and serve important biological roles. Hydrogen cyanide, traditionally considered a cytotoxic molecule in mammals, serves as an endogenous mediator in several plants and bacterial species. Here we show that low concentrations of cyanide are generated endogenously in mouse liver and human hepatocytes. Cyanide production is stimulated by glycine, occurs at the low pH of lysosomes and requires peroxidase activity. Cyanide, in turn, is detectable in several cellular compartments. Cyanide is also detectable basally in the blood of mice; its levels increase after treatment of the animals with glycine. Rhodanese activity regulates endogenous cyanide levels. Cyanide, when generated endogenously at an optimal level, exerts stimulatory effects on mitochondrial bioenergetics, cell metabolism and cell proliferation. Dysregulation of endogenous cyanide, either below or above optimal levels, impairs cellular bioenergetics. The regulatory effects of cyanide are in part mediated by posttranslational modification of cysteine residues via protein cyanylation; cyanylated protein residues can be detected basally, and increase after treatment with glycine. Controlled low-dose cyanide supplementation exhibits cytoprotective effects, as demonstrated in hypoxia and reoxygenation models in vitro and in vivo. However, pathologically elevated cyanide production, as demonstrated in nonketotic hyperglycinemia - an autosomal recessive disease of glycine metabolism - is deleterious to the cells.

biochemistry↗