Disruption of iron homeostasis increases phosphine toxicity in caenorhabditis elegans

The aim of this study is to identify the biochemical mechanism of phosphine toxicity and resistance, using Caenorhabditis elegans as a model organism. To date, the precise mode of phosphine action is unclear. In this report, we demonstrate the following dose-dependent actions of phosphine, in vitro: (1) reduction of ferric iron (Fe3+) to ferrous iron (Fe2+), (2) release of iron from horse ferritin, (3) and the peroxidation of lipid as a result of iron release from ferritin. Using in situ hybridization, we show that the ferritin genes of C. elegans, both ferritin-1 and ferritin-2, are expressed along the digestive tract with greatest expression at the proximal and distal ends. Basal expression of the ferritin-2 gene, as determined by quantitative PCR, is approximately 80 times that of ferritin-1. However, transcript levels of ferritin-1 are induced at least 20-fold in response to phosphine, whereas there is no change in the level of ferritin-2. This resembles the reported pattern of ferritin gene regulation by iron, suggesting that phosphine toxicity may be related to an increase in the level of free iron. Indeed, iron overload increases phosphine toxicity in C. elegans at least threefold. Moreover, we demonstrate that suppression of ferritin-2 gene expression by RNAi, significantly increases sensitivity to phosphine. This study identifies similarities between phosphine toxicity and iron overload and demonstrates that phosphine can trigger iron release from storage proteins, increasing lipid peroxidation, leading to cell injury and/or cell death.

Comparison of the impact of six heat-load management strategies on thermal responses and milk production of feed-pad and pasture fed dairy cows in a subtropical environment

Exposure to hot environments affects milk yield (MY) and milk composition of pasture and feed-pad fed dairy cows in subtropical regions. This study was undertaken during summer to compare MY and physiology of cows exposed to six heat-load management treatments. Seventy-eight Holstein-Friesian cows were blocked by season of calving, parity, milk yield, BW, and milk protein (%) and milk fat (%) measured in 2 weeks prior to the start of the study. Within blocks, cows were randomly allocated to one of the following treatments: open-sided iron roofed day pen adjacent to dairy (CID) + sprinklers (SP); CID only; non-shaded pen adjacent to dairy + SP (NSD + SP); open-sided shade cloth roofed day pen adjacent to dairy (SCD); NSD + sprinkler (sprinkler on for 45 min at 1100 h if mean respiration rate >80 breaths per minute (NSD + WSP)); open-sided shade cloth roofed structure over feed bunk in paddock + 1 km walk to and from the dairy (SCP + WLK). Sprinklers for CID + SP and NSD + SP cycled 2 min on, 12 min off when ambient temperature >26°C. The highest milk yields were in the CID + SP and CID treatments (23.9 L cow−1 day−1), intermediate for NSD + SP, SCD and SCP + WLK (22.4 L cow−1 day−1), and lowest for NSD + WSP (21.3 L cow−1 day−1) (P < 0.05). The highest (P < 0.05) feed intakes occurred in the CID + SP and CID treatments while intake was lowest (P < 0.05) for NSD + WSP and SCP + WLK. Weather data were collected on site at 10-min intervals, and from these, THI was calculated. Nonlinear regression modelling of MY × THI and heat-load management treatment demonstrated that cows in CID + SP showed no decline in MY out to a THI break point value of 83.2, whereas the pooled MY of the other treatments declined when THI >80.7. A combination of iron roof shade plus water sprinkling throughout the day provided the most effective control of heat load.