Chronic tubulointerstitial nephropathy (CTIN) is one of the most common kidney diseases. However, treatment for CTIN has multiple limits. Adjuvant therapy through nutritional regulation has become a hot research topic at present. Icariin (ICA), an extraction of Chinese herbal medicine epimedium, has many pharmacological functions including anti-inflammation and tonifying kidney. Selenomethionine (SeMet) possesses the effects of antioxidant and lightening nephrotoxicity. However, little is known about the combined nephroprotection of them. This study was investigated to evaluate the joint effects of ICA and SeMet on CTIN and explore the mechanism. Based on a novel CTIN model developed in our previous study, mice were randomly divided into five groups (a: control; b: model; c: model + ICA; d: model + SeMet; e: model + ICA + SeMet). Renal tubule epithelial cells were treated with cyclosporine A and ochratoxin A without/with ICA or/and SeMet. The results showed that ICA or/and SeMet ameliorated CTIN by inhibiting the uptrends of blood urine nitrogen, serum creatinine, urine protein, urine gravity, histopathological damage degree and collagen I deposition. ICA or/and SeMet also increased cell proliferation and decreased apoptosis and the expression of transforming growth factor-beta 1 and α-smooth muscle actin. Emphatically, ICA and SeMet joint had better nephroprotection than alone in most indexes including fibrosis. Furthermore, ICA and SeMet joint decreased the activation of toll-like receptor 4 (TLR4)/NFκB pathway induced by CTIN. TLR4 overexpression counteracted the joint protection of ICA and SeMet. Therefore, ICA and SeMet in combination could protect against CTIN through blocking TLR4/NFκB pathway. The study will provide novel insights to explore an adjuvant therapeutic orientation.

The presence of certain mycotoxins within poultry feed has a negative impact upon the growth and the quality of the final product in the form of meat and eggs. More than 300 different chemically diverse mycotoxins have been identified, but ochratoxins and aflatoxins are considered to be most harmful to the poultry industry. Ochratoxin, more importantly ochratoxin A (OTA) is produced by different species of Aspergillus and Penicillium spp. which are present as storage fungi within the stored grains and feed ingredients. Body weight gain has been found to decrease in a dose dependent manner when infected at rates of 0.5-29.4 mg/kg for 7-60 days in different experimental studies. Decreased feed intake has been observed at levels of 0.5-4 mg/kg OTA fed for 21-60 days, while egg production, hatchability, eggshell thickness and egg mass production is severely affected when 0.5-4 mg/kg OTA in feed was fed for 28-84 days. However, 0.5-20 mg/kg OTA given for between two and 10 weeks of age was sufficient to produce histopathological alterations in the liver, kidney, thymus, bursa of Fabricius, spleen, lungs and heart. The research shows that OTA adversely affects every organ in birds and, in the following review, OTA associated alterations in growth parameters, production performance and histopathological disturbances of different body organs are discussed.

Curcumin has been attributed with antioxidant, anti-inflammatory, antibacterial activities, and has shown highly protective effects against enteropathogenic bacteria and mycotoxins. Ochratoxin A (OTA) is one of the major intestinal pathogenic mycotoxins. The possible effect of curcumin on the alleviation of enterotoxicity induced by OTA is unknown. The effects of dietary curcumin supplementation on OTA-induced oxidative stress, intestinal barrier and mitochondrial dysfunctions were examined in young ducks. A total of 540 mixed-sex 1-day-old White Pekin ducklings with initial BW (43.4±0.1 g) were randomly assigned into controls (fed only the basal diet), a group fed an OTA-contaminated diet (2 mg/kg feed), and a group fed the same OTA-contaminated feed plus 400 mg/kg of curcumin. Each treatment consisted of six replicates, each containing 30 ducklings and treatment lasted for 21 days. There was a significant decrease in average daily gain (ADG) and increased feed : gain caused by OTA (P<0.05); curcumin co-treatment prevented the decrease in BW and ADG compared with the OTA group (P<0.05). Histopathological and ultrastructural examination showed clear signs of enterotoxicity caused by OTA, but these changes were largely prevented by curcumin supplementation. Curcumin decreased the concentrations of interleukin-1β, tumor necrosis factor-α and malondialdehyde, and increased the activity of glutathione peroxidase induced by OTA in the jejunal mucosa of ducks (P<0.05). Additionally, curcumin increased jejunal mucosa occludin and tight junction protein 1 mRNA and protein levels, and decreased those of ρ-associated protein kinase 1 (P<0.05). Notably, curcumin inhibited the increased expression of apoptosis-related genes, and downregulated mitochondrial transcription factors A, B1 and B2 caused by OTA without any effects on RNA polymerase mitochondrial (P<0.05). These results indicated that curcumin could protect ducks from OTA-induced impairment of intestinal barrier function and mitochondrial integrity.

Mice fed 1·5 mg ochratoxin A (OTA) per kg body weight and infected with Trypanosoma brucei rhodesiense were compared with trypanosome-infected placebo-fed and uninfected OTA-fed controls. Uninfected OTA-fed mice showed fever, lethargy, facial and eyelid oedemas, mild hepatitis and nephritis, and high survival. Infected placebo-fed controls had mean pre-patent period (PPP) of 3·26 days, lethargy, dyspnoea, fever, facial and scrotal oedema, survival of 33–65 days, reduced red cell counts (RCC: 10·96–6·87×106 cells/μl of blood), packed cell volume (PCV: 43·19–26·36%), haemoglobin levels (Hb: 13·37–7·92 g/dL) and mean corpuscular volume (MCV) of 37·96–41·31 fL, hepatosplenomegaly, generalized oedemas, heart congestion, hepatitis and nephritis. Compared to infected placebo-fed controls, infected OTA-fed mice had significantly (P<0·05) shorter mean PPP (2·58 days), reduced survival (6–47 days), more pronounced fever and dyspnoea. The latter had significantly (P<0·05) reduced RCC (10·74–4·56×106 cells/μl of blood), PCV (43·90–20·78%), Hb (13·06–5·74 g/dL), increased MCV (39·10–43·97 fL), severe generalized oedemas, haemorrhages, congestion, hepatic haemosiderosis, hepatitis, nephritis, endocarditis, pericarditis and exclusively, splenic macrophage and giant cell hyperplasia, expanded red pulp and splenic erythrophagocytosis. It was concluded that OTA aggravated the pathogenesis of T. b. rhodesiense infection in mice, and should therefore be taken into consideration during trypanosomosis control programmes.

The aim of the present study was to verify whether the oral administration of cyanidin 3-O-β-d-glucoside (C3G) might counteract damage induced by chronic exposure (28 d) to ochratoxin A (OTA) in rats and if its effect may be mediated by haeme oxygenase-1 (HO-1). Forty male Sprague–Dawley rats, individually caged, were divided into four groups of ten animals. A control group received a commercial diet, group C3G received the control diet supplemented with C3G (1 g/kg feed), group OTA received the control diet supplemented with 200 parts per billion of OTA, and group OTA+C3G received the OTA group diet supplemented with C3G (1 g/kg feed). After 4 weeks of treatment animals were killed and the liver, kidneys and brain of each rat were collected and homogenised to evaluate non-proteic thiol groups (RSH), lipid hydroperoxide (LOOH) levels, HO-1 expression and DNA fragmentation. Rats of the OTA group showed a significant (P < 0·001) decrease in RSH content of kidney and liver and a significant (P < 0·001) increase of LOOH in all the examined tissues compared with the control group. In the OTA+C3G group both RSH content and LOOH levels were similar to those observed in the control group, demonstrating that C3G was able to counteract the effects of OTA. A significant (P < 0·001) induction of HO-1 was evident in kidney and liver of both OTA and C3G groups. DNA damage occurred in all the examined tissues of the OTA group, whereas C3G was able to prevent it. The present study confirmed that the effects of OTA are mediated by oxidative stress and demonstrated that C3G efficiently counteracted deleterious effects of OTA because of its antioxidant and HO-1-inducing properties.

Ochratoxin A (OTA), a mycotoxin frequently present in food and feedstuffs, produces a wide range of toxic effects, including cell death via lipid peroxidation. In one human and four animal cell lines we determined the half lethal concentration (LC50) of OTA, its effect on reactive oxygen species (ROS) production, and its ability to induce cytochrome p450 activity. We also examined the protective effect of α-tocopherol and all-trans-retinol in the most sensitive cell lines (i.e. bovine mammary epithelia, for which LC50 was 0·8μg/ml (24h), and Madin Darby canine kidney, for which LC50 was 4·3μg/ml (48h)). Pre-incubation for 3h with either antioxidant significantly (P<0·05) ameliorated the OTA-induced reduction in cell viability and significantly decreased (P<0·05) ROS production. These findings indicate that oxidative stress is an important factor in OTA cytotoxicity. Supplementation with antioxidant molecules may counteract the short-term toxicity of this mycotoxin.

The avian kidney has shown a remarkable ability to maintain adequate and even normal function in the face of a mycotoxin challenge. Full evaluation of the nephrotoxicity of a substance must therefore go beyond pathological and ultrastructural documentation and include a complete functional evaluation. To date, only three nephrogenic mycotoxins, citrinin, ochratoxin A, and aflatoxin B1 have been assessed for their ability to alter avian renal function. At non-lethal doses, citrinin appears to have acute reversible effects on the distal portion of the nephron, possibly acting to inhibit water absorption. Ochratoxin A is more potent and less acute than citrinin but less site-specific in that both proximal and distal tubules are damaged, resulting in severe loss of both fluids and electrolytes. Aflatoxin B1 at a dosage and duration which induced hepatotoxicity, concurrently exerted nephrogenic effects such as increased urinary calcium excretion and decreased inorganic phosphate excretion. In commercial broilers aflatoxin B1 has been shown to decrease plasma levels of 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D and may also decrease endogenous parathyroid hormone synthesis and the renal sensitivity to parathyroid hormone. Furthermore, exposure to aflatoxin B1 may cause prolonged alteration in renal function such as reduced glomerular filtration rate. This review summarizes the studies which have been conducted to evaluate avian renal function during both acute and chronic exposure to these three mycotoxins.