Organophosphates (OPs) are toxic chemicals produced by an esterification process and some other routes. They are the main components of herbicides, pesticides, and insecticides and are also widely used in the production of plastics and solvents. Acute or chronic exposure to OPs can manifest in various levels of toxicity to humans, animals, plants, and insects. OPs containing insecticides were widely used in many countries during the 20th century, and some of them continue to be used today. In particular, 36 OPs have been registered in the USA, and all of them have the potential to cause acute and sub-acute toxicity. Renal damage and impairment of kidney function after exposure to OPs, accompanied by the development of clinical manifestations of poisoning back in the early 1990s of the last century, was considered a rare manifestation of their toxicity. However, since the beginning of the 21st century, nephrotoxicity of OPs as a manifestation of delayed toxicity is the subject of greater attention of researchers. In this article, we present a modern view on the molecular pathophysiological mechanisms of acute nephrotoxicity of organophosphate compounds.

The present study aimed to explore the consequences of a single exposure to a social defeat on dopamine release in the rat nucleus accumbens measured with a fast-scan cyclic voltammetry. We found that 24 h after a social defeat, accumbal dopamine responses, evoked by a high frequency electrical stimulation of the ventral tegmental area, were more profound in socially defeated rats in comparison with non-defeated control animals. The enhanced dopamine release was associated with the prolonged immobility time in the forced swim test. The use of the dopamine depletion protocol revealed no alteration in the reduction and recovery of the amplitude of dopamine release following social defeat stress. However, administration of dopamine D2 receptor antagonist, raclopride (2 mg/kg, i.p.), resulted in significant increase of the electrically evoked dopamine release in both groups of animals, nevertheless exhibiting less manifested effect in the defeated rats comparing to control animals. Taken together, our data demonstrated profound alterations in the dopamine transmission in the association with depressive-like behavior following a single exposure to stressful environment. These voltammetric findings pointed to a promising path for the identification of neurobiological mechanisms underlying stress-promoted behavioral abnormalities.

Spinal cord injury (SCI) is one of the most frequent causes of disability, accompanied by motor and postural impairments, as well as autonomic and behavioural disorders. Since the beginning of the last century, researchers have been developing and refining experimental models of SCI to study pathogenesis and find therapies. Since the beginning of the 20th century, quite a wide range of methods have been developed for contusion and compression injury, complete and partial transection of the spinal cord, and many others. The choice of model subject in such studies was not limited to mammals, but also included amphibians, lampreys, and even fish. Many functional tests have been proposed to assess functional recovery after injury in laboratory animals, ranging from simple rating scales to locomotion kinematics or recording of spinal neuronal activity. This review describes existing models of SCI in most animal species used in neurobiology. Their key characteristics are discussed, which determine the choice of model and model animals depending on the experimental tasks. Each experimental model of SCI has its own advantages and disadvantages determined by species-specific features of spinal cord anatomy and physiology, the speed of recovery from injury, and the ratio of the necrosis zone to the penumbra. The applicability and availability of the proposed methods for assessing the speed and completeness of recovery is also an important factor.

The delayed effects of acute intoxication by organophosphates (OPs) are poorly understood, and the various experimental animal models often do not take into account species characteristics. The principal biochemical feature of rodents is the presence of carboxylesterase in blood plasma, which is a target for OPs and can greatly distort their specific effects. The present study was designed to investigate the nephrotoxic effects of paraoxon (O,O-diethyl O-(4-nitrophenyl) phosphate, POX) using three models of acute poisoning in outbred Wistar rats. In the first model (M1, POX2x group), POX was administered twice at doses 110 µg/kg and 130 µg/kg subcutaneously, with an interval of 1 h. In the second model (M2, CBPOX group), 1 h prior to POX poisoning at a dose of 130 µg/kg subcutaneously, carboxylesterase activity was pre-inhibited by administration of specific inhibitor cresylbenzodioxaphosphorin oxide (CBDP, 3.3 mg/kg intraperitoneally). In the third model (M3), POX was administered subcutaneously just once at doses of LD16 (241 µg/kg), LD50 (250 µg/kg), and LD84 (259 µg/kg). Animal observation and sampling were performed 1, 3, and 7 days after the exposure. Endogenous creatinine clearance (ECC) decreased in 24 h in the POX2x group (p = 0.011). Glucosuria was observed in rats 24 h after exposure to POX in both M1 and M2 models. After 3 days, an increase in urinary excretion of chondroitin sulfate (CS, p = 0.024) and calbindin (p = 0.006) was observed in rats of the CBPOX group. Morphometric analysis revealed a number of differences most significant for rats in the CBPOX group. Furthermore, there was an increase in the area of the renal corpuscles (p = 0.0006), an increase in the diameter of the lumen of the proximal convoluted tubules (PCT, p = 0.0006), and narrowing of the diameter of the distal tubules (p = 0.001). After 7 days, the diameter of the PCT lumen was still increased in the nephrons of the CBPOX group (p = 0.0009). In the M3 model, histopathological and ultrastructural changes in the kidneys were revealed after the exposure to POX at doses of LD50 and LD84. Over a period from 24 h to 3 days, a significant (p = 0.018) expansion of Bowman’s capsule was observed in the kidneys of rats of both the LD50 and LD84 groups. In the epithelium of the proximal tubules, stretching of the basal labyrinth, pycnotic nuclei, and desquamation of microvilli on the apical surface were revealed. In the epithelium of the distal tubules, partial swelling and destruction of mitochondria and pycnotic nuclei was observed, and nuclei were displaced towards the apical surface of cells. After 7 days of the exposure to POX, an increase in the thickness of the glomerular basement membrane (GBM) was observed in the LD50 and LD84 groups (p = 0.019 and 0.026, respectively). Moreover, signs of damage to tubular epithelial cells persisted with blockage of the tubule lumen by cellular detritus and local destruction of the surface of apical cells. Comparison of results from the three models demonstrates that the nephrotoxic effects of POX, evaluated at 1 and 3 days, appear regardless of prior inhibition of carboxylesterase activity.