The population of Indian vultures has been rapidly declining since 2003. This is attributed to the diclofenac present in the carcasses which the vultures eat. Vultures seem to digest all sorts of food items but why can't they digest diclofenac? What is the mechanism which causes this?
Post-mortem examination revealed extensive visceral gout in all diclofenac-treated birds (see electronic supplementary material). Histological examination revealed significant lesions in the kidneys, liver and spleen with extensive uric acid crystal deposition.
From the mechanistic studies both diclofenac and meloxicam were directly toxic to chicken and vulture renal tubular epithelial cells following 48h of incubation. It was later shown that this toxicity was associated with an increased production of reactive oxygen species (ROS), which could be temporarily ameliorated by pre-incubation with uric acid due to its anti-oxidant activity. When cultures were incubated with either drug for only two hours, meloxicam showed no toxicity in contrast to the cellular toxicity present for diclofenac. In both cases no increase in ROS production was evident. In addition, diclofenac influenced the excretion of uric acid by interfering with p-amino-hippuric acid channels. The effect on uric acid excretion persisted after the removal of the diclofenac. It was therefore concluded that vulture susceptibility to diclofenac results from a combination of an increase in cellular ROS, a depletion of intracellular uric acid concentration and most importantly the drug’s long half-life in the vulture.
The second link posits three mechanisms for the cause of renal failure in vultures (ref., pg. 26):
- Ischaemic nephropathy with secondary visceral gout
- Organic Anion Transporter antagonism
- Secondary renal toxicity with or without toxic activation
6$\begingroup$ I'm just coming across this post now and I don't see any downvotes. As such, I'm going to remove your last comment as no longer necessary. Your post is well-linked/supported, so that aspect is great (thanks!) and should discourage downvoters. However, to further discourage downvoting, I would also encourage (if you'd like) to add a bit more non-quote context to your post. Some users downvote due to seeing answers that are primarily quotes of other sources. But as I said, you don't currently have any downvotes so you might be ok as is. Thanks! $\endgroup$ Feb 21, 2020 at 19:24
4$\begingroup$ I just seem to be the victim of some drive-by downvoters, lately, and am trying to head it off at the pass. Sorry if this annoys some. $\endgroup$ Feb 22, 2020 at 1:50
7$\begingroup$ Everyone is a "drive-by downvoter" by your definition. No one is ever supposed to comment on how they voted; votes are anonymous, and disclosing how you voted would defeat the anonymity of the system. Leaving comments does nothing to "head off" the problem because it isn't a problem. A downvote means someone who read your answer thought it was unclear or not useful. That's all. $\endgroup$ Feb 22, 2020 at 5:06