Chronic Intestinal Disorders in Humans and Pets: Current Management and the Potential of Nutraceutical Antioxidants as Alternatives.

Chronic intestinal disorders (CID) are characterized by persistent, or recurrent gastrointestinal (GI) signs present for at least three weeks. In human medicine, inflammatory bowel disease (IBD) is a group of chronic GI diseases and includes Crohn's disease (CD) and ulcerative colitis (UC). On the other hand, the general term chronic enteropathies (CE) is preferred in veterinary medicine. Different therapeutic approaches to these diseases are used in both humans and pets. This review is focused on the use of traditional therapies and nutraceuticals with specific antioxidant properties, for the treatment of CID in humans and animal patients. There is strong evidence of the antioxidant properties of the nutraceuticals included in this review, but few studies report their use for treating CID in humans and none in animals. Despite this fact, the majority of the nutraceuticals described in the present article could be considered as promising alternatives for the regular treatment of CID in human and veterinary medicine.

Efficacy of a dietary supplement in dogs with osteoarthritis: A randomized placebo-controlled, double-blind clinical trial.

This study is a randomized, placebo-controlled, double-blinded trial performed to investigate the effects of a dietary supplement containing a mixture of Boswellia serrata Roxb., chlorophyll, green tea extract, glucosamine, chondroitin sulfate, hyaluronic acid, and further in the manuscript: non-hydrolised type II collagen in dogs with osteoarthritis (OA). A total of 40 dogs were enrolled in the study, they were randomly divided in control (CTR) and treatment (TRT) groups. The TRT group received the dietary supplement for 60 days. The CTR group received a placebo for the same number of days. All the subjects had veterinary evaluations during the trial and owners were requested to fill in questionnaires on chronic pain using the Helsinki Chronic Pain Index. The product was easy to administer and no side effects were reported. Combining results from veterinarian and owner evaluations, the tested product proved to be significantly beneficial in alleviating pain and in reducing the clinical signs in dogs with OA.

Chronic Kidney Disease and Dietary Supplementation: Effects on Inflammation and Oxidative Stress.

Chronic kidney disease (CKD) causes an irreversible loss of kidney functioning in dogs. This double-blind case-control study evaluates the efficacy of a dietary supplement, which contains calcium carbonate, calcium lactate-gluconate, chitosan, sodium bicarbonate, Lactobacillus acidophilus D2/CSL, Olea europaea L. extract, and fructooligosaccharides, in dogs in advanced CKD stage. Thirty dogs were enrolled in the study; half were administered the new dietary supplementation for 90 days, while the others were used as controls. Hematologic, biochemical, and urinalysis were performed. This novel dietary supplement mainly reported a good control of uremia, phosphate, acid-base balance, blood pressure, inflammation, and oxidative stress in dogs with advanced stages of CKD.

In vitro activity of lactoferricin solution against Malassezia pachydermatis from otitis externa in dogs and cats.

BACKGROUND: Malassezia pachydermatis is a commensal organism of the skin, yet it may induce dermatitis and/or otitis. Lactoferricin (Lfcin) is an antimicrobial peptide obtained by the pepsin-mediated digestion of lactoferrin, a multifunctional innate-defence milk protein. The antibacterial activity of Lfcin is thought to cause alteration of bacterial membrane permeability, thus inducing cell death. OBJECTIVES: The aim of this study was to evaluate in vitro antifungal activity of different dilutions of Lfcin solution against M. pachydermatis strains isolated from ears of dogs and cats with otitis externa. METHODS AND MATERIALS: Fifty clinical Malassezia isolates from 40 dogs and 10 cats were tested. A dilution method in microtitre plates was used starting with a 20% Lfcin water solution. The different dilutions were 2:1 (13.3%), 1:1 (10%), 1:2 (6.7%), 1:5 (3.3%) and 1:10 (1.8%). Results were expressed as the value at which the growth of 50% (minimal fungicidal concentration MFC50 ) and 90% (MFC90 ) of yeast cells was inhibited. RESULTS: All strains showed susceptibility to 20% Lfcin solution (100%). With 1:5 and 1:10 dilutions corresponding to 3.3% and 1.8% Lfcin solutions, all strains showed resistance. The MFC50 and MFC90 values were observed at 13.3% and 20% Lfcin solutions. CONCLUSIONS AND CLINICAL RELEVANCE: The results indicated that Lfcin solution exhibits the antimicrobial activity specific to antimicrobial peptides. In particular, the 20% solution can be effective in killing M. pachydermatis isolated strains. Some susceptibilities also are evident at lower concentrations of ≤6.7% for four strains.

Superoxide Dismutase Administration: A Review of Proposed Human Uses.

Superoxide dismutases (SODs) are metalloenzymes that play a major role in antioxidant defense against oxidative stress in the body. SOD supplementation may therefore trigger the endogenous antioxidant machinery for the neutralization of free-radical excess and be used in a variety of pathological settings. This paper aimed to provide an extensive review of the possible uses of SODs in a range of pathological settings, as well as describe the current pitfalls and the delivery strategies that are in development to solve bioavailability issues. We carried out a PubMed query, using the keywords "SOD", "SOD mimetics", "SOD supplementation", which included papers published in the English language, between 2012 and 2020, on the potential therapeutic applications of SODs, including detoxification strategies. As highlighted in this paper, it can be argued that the generic antioxidant effects of SODs are beneficial under all tested conditions, from ocular and cardiovascular diseases to neurodegenerative disorders and metabolic diseases, including diabetes and its complications and obesity. However, it must be underlined that clinical evidence for its efficacy is limited and consequently, this efficacy is currently far from being demonstrated.

Strategies to expand the therapeutic potential of superoxide dismutase by exploiting delivery approaches.

The overproduction of free radicals can cause oxidative-stress damage to a range of biomolecules, and thus potentially contribute to several pathologies, from neurodegenerative disorders to cardiovascular diseases and metabolic disorders. Endogenous antioxidant enzymes, such as superoxide dismutase (SOD), play an important role in diminishing oxidative stress. SOD supplementation could therefore be an effective preventive strategy to reduce the risk of free-radical overproduction. However, the efficacy of SOD administration is hampered by its rapid clearance. Several different approaches to improve the bioavailability of SOD have been explored in recent decades. This review intends to describe the rationale that underlie the various approaches and chemical strategies that have led to the most recent advances in SOD delivery. This critical description includes SOD conjugates, SOD loaded into particulate carriers (micelles, liposomes, nanoparticles, microparticles) and the most promising and suitable formulations for oral delivery, with a particular emphasis on reports of preclinical/clinical results. Likely future directions are also considered and reported.

Lactoferrin-derived peptides antimicrobial activity: an in vitro experiment.

Antibiotic resistance is a global problem, searching for new antimicrobial agents is an urgent need. In this study, in vitro antibacterial and antimicrobial effects of milk-derived antimicrobial agents, lactoferrin-derived peptides, lactoferricin (Lfc) and lactoferrampin (Lfa) (alone or in combination) and their association with natural extracts have been explored. The assessment of antimicrobial activity was based on two measurements: Minimum Inhibitory Concentration and Fractional Inhibitory Concentration indexes. Lfc alone is more suitable for inhibiting Staphylococcus intermedius and Malassezia pachydermatis, while Lfa against Candida albicans, a synergistic effect of the two peptides against all the three pathogens has been detected. A strong synergy of all the natural extracts with Lfc and Lfa solution against selected microorganisms in vitro was pointed out. Our results suggest that natural-derived compounds, such as milk peptides and vegetal extracts could be promising tools to treat moderate fungal and bacterial infections.

Efficacy of a new dietary supplement in dogs with advanced chronic kidney disease.

Chronic kidney disease (CKD) is a common disease in elderly dogs. The present study aims to evaluate the efficacy of a dietary supplement containing calcium carbonate, calcium-lactate gluconate, chitosan and sodium bicarbonate in dogs with IRIS stage 3 of CKD. Twenty dogs were enrolled in the study, ten were administered the new dietary supplementation for 180 days (T group) while the others were used as control group (C group). Haematologic, biochemical and urinalysis were performed every 30 days. A significant reduction in the T group compared to the C group in serum phosphorus level and increase in serum bicarbonate and ionized calcium values were recorded. The urine protein-to-creatinine ratio (UPC) was significantly lower in the T group at the end of the study compared to the C group. The tested supplement could be considered as a supportive treatment for dogs with advanced CKD.

Preparation and characterization of cyclodextrin nanosponges for organic toxic molecule removal.

Cyclodextrin-based nanosponges (CD-NS) are considered as safe and biocompatible systems for removing toxic molecules from the body. Rapid removal of toxic molecules that are formed in the body from certain food constituents, is relevant especially for patients affected by chronic kidney disease. Within the scope of this study, innovative cyclodextrin polymers were synthesized to form nanosponges able to remove indole, before it could form the toxic indoxyl sulfate in the body. Furthermore, in vivo studies were carried out using the two optimal CD-NS formulations by assessing physicochemical properties, stability, indole adsorption capacity and in vitro cytotoxicity. NS prepared from ß-cyclodextrin cross-linked with toluene diisocyanate was found to be the most effective NS with an in vitro indole adsorption capacity of over 90%. In addition, this derivative was more stable in gastrointestinal media. Animal studies further revealed that oral CD-NSs did not tend to accumulate and damage gastrointestinal tissues and are excreted from the GI tract with minimal absorption. In conclusion, this study suggests that CD-NS formulations are effective and safe in removing toxic molecules from the body. Their potential use in veterinary or human medicine could reduce dialysis frequency and avoid hepatic and cardiac toxicity avoiding the indole formation.

Effects of probiotic Lactobacillus acidophilus D2/CSL (CECT 4529) on the nutritional and health status of boxer dogs.

BACKGROUND: The aim of the present study was to investigate the effects of Lactobacillus acidophilus D2/CSL (CECT 4529) probiotic strain on nutritional status and faecal and microbiological parameters in a group of purebred boxers. METHODS: Forty healthy adult boxer dogs were randomly assigned to a treated (LACTO) group receiving a commercial diet supplemented with L acidophilus D2/CSL (CECT 4529) to a final concentration of 5.0 x 109 colony-forming unit/kg of food, and a control (CTR) group receiving the same diet but without the probiotic (placebo). Nutritional status (body weight, skinfold thickness, body condition score) and faecal quality parameters were analysed. RESULTS: No differences in body weight and skin thickness were found during the whole experimental period. Dogs in the LACTO group showed a significantly higher body condition score than those in the CTR group (4.86±0.55 v 4.65±0.65), and no significant differences were recorded in body weight and skinfold thickness. The LACTO group showed a significantly lower faecal moisture (in per cent) compared with the CTR group (0.67±0.007 v 0.69±0.007). Faecal hardness (in kg) was higher in the LACTO group than in the CTR group (0.86±0.047 v 0.70±0.051), and faecal score also improved in the LACTO group (3.78±0.95 v 4.25±0.91). A significant difference in total Escherichia coli counts as well as in lactobacilli counts between the CTR and LACTO groups was only detected at 28 days. CONCLUSION: Supplementation of L acidophilus D2/CSL (CECT 4529) significantly improved the nutritional status and faecal parameters of dogs.

Effects of Lactobacillus acidophilus D2/CSL (CECT 4529) supplementation on healthy cat performance.

BACKGROUND: The present study aimed to evaluate the effects of the probiotic strain Lactobacillus acidophilus D2/CSL (CECT 4529) on nutritional condition and faecal quality in cats. METHODS: Ten healthy adult cats from the same cattery were included (aged >9 months; male:female sex ratio=3:7). The animals were randomly assigned to a control group (CTR; n=5; male:female=1:4; room 1: 16 m2) and to a treated group (LACTO; n=5; male:female=2:3; room 2: 16 m2) receiving the same commercial dry diet. The LACTO group diet was supplemented with the probiotic (5 x 109 cfu/kg feed at least). A five-week experimental period was applied, and nutritional status was monitored by bodyweight (BW) and body condition score (BCS). Faecal quality was evaluated using faecal score (FS) and faecal moisture (FM) parameters. Plate counts of some faecal bacteria species were carried out. The data obtained were analysed using MIXED, GLM and NPAR1WAY procedures (SAS V.9.4; P≤0.05). RESULTS: The two groups did not show differences in BW and BCS data. A clear effect of the probiotic supplementation on FM was recorded (LACTO 44 per cent v CTR group 46 per cent; P=0.04). FS in the LACTO group (3.35) was close to ideal values (2-3) in comparison with the CTR group (3.75). Positive effects of L acidophilus D2/CSL have been recorded in terms of increase in faecal lactobacilli counts and reduction in faecal coli counts. CONCLUSIONS: This study's preliminary results describe how inclusion of L acidophilus D2/CSL (CECT 4529) probiotic strain in cats' diets could effectively improve faecal quality parameters and consequently gut health in adult healthy cats.

Investigation of hallmarks of carbonyl stress and formation of end products in feline chronic kidney disease as markers of uraemic toxins.

OBJECTIVES: Cats are commonly affected by chronic kidney disease (CKD). Many reactive carbonyl intermediates and end products originating from the oxidative stress pathways are recognised as uraemic toxins and may play a role in CKD progression. The aim of the present study is to confirm whether carbonyl end-product formation is higher in cats affected by CKD and to assess whether an angiotensin-converting enzyme inhibitor (ACEi) might affect these hallmarks. METHODS: Twenty-two cats were divided into three groups: a control group (CG), cats with CKD and cats with CKD treated with an ACEi. Serum levels of pentosidine, carboxymethyllysine, advanced oxidation protein products, malondialdehyde, methylglyoxal and hexanoyl-lysine were measured. In addition, biochemical parameters and systolic blood pressure were evaluated. After checking for normality, comparisons between groups were performed followed by multiple comparison tests. P values ⩽0.05 were considered significant. Correlations between concentrations of the considered biomarkers and of the other metabolic parameters were investigated. RESULTS: Advanced oxidation protein products, malondialdehyde and hexanoyl-lysine concentrations were significantly higher in CKD and ACEi-treated groups compared with the CG ( P <0.05). Carboxymethyllysine increased in the ACEi-treated group when compared with the CG, whereas intermediate values of these biomarkers were found in the CKD group ( P <0.05). The ACEi-treated group showed the highest values of carboxymethyllysine, advanced oxidation protein products and hexanoyl-lysine. By contrast, the CKD group had the highest concentration of malondialdehyde. No statistically significant difference was found in the levels of pentosidine or methylglyoxal. End products correlated with creatinine and urea and with each other. CONCLUSIONS AND RELEVANCE: Significantly high concentrations of both intermediate and end products of carbonyl/oxidative stress were detected in CKD cats. This is the first study to have concurrently taken into account several uraemic toxins and biochemical parameters in cats affected by CKD.

Cannabinoid Delivery Systems for Pain and Inflammation Treatment.

There is a growing body of evidence to suggest that cannabinoids are beneficial for a range of clinical conditions, including pain, inflammation, epilepsy, sleep disorders, the symptoms of multiple sclerosis, anorexia, schizophrenia and other conditions. The transformation of cannabinoids from herbal preparations into highly regulated prescription drugs is therefore progressing rapidly. The development of such drugs requires well-controlled clinical trials to be carried out in order to objectively establish therapeutic efficacy, dose ranges and safety. The low oral bioavailability of cannabinoids has led to feasible methods of administration, such as the transdermal route, intranasal administration and transmucosal adsorption, being proposed. The highly lipophilic nature of cannabinoids means that they are seen as suitable candidates for advanced nanosized drug delivery systems, which can be applied via a range of routes. Nanotechnology-based drug delivery strategies have flourished in several therapeutic fields in recent years and numerous drugs have reached the market. This review explores the most recent developments, from preclinical to advanced clinical trials, in the cannabinoid delivery field, and focuses particularly on pain and inflammation treatment. Likely future directions are also considered and reported.

Lactoferricin/verbascoside topical emulsion: a possible alternative treatment for atopic dermatitis in dogs.

Atopic dermatitis affects 3-15% of the general dog population and it has been diagnosed by veterinarians up to 58% of dogs affected with skin disease. It is usually a life-long pathology which can be controlled, but it can be seldom cured. The present investigation describes a case study in which lactoferricin and verbascoside are part of a formulation to obtain a dermatological lotion for canine dermatitis treatment. The study was an open-label trial design of two-week treatment. Thirty-eight dogs (23 females and 15 males), with atopic dermatitis and secondary bacterial or yeast overgrowth have been included. During treatment period the total clinical score progressively decreased associated with an improvement in clinical signs. No adverse effects were reported in any of the treated dogs. The present research suggests that daily applications of tested emulsion are effective in reducing bacterial overgrowth and clinical signs in skin folds and atopic dermatitis.

Nanostructured delivery systems with improved leishmanicidal activity: a critical review.

Leishmaniasis is a vector-borne zoonotic disease caused by protozoan parasites of the genus Leishmania, which are responsible for numerous clinical manifestations, such as cutaneous, visceral, and mucocutaneous leishmaniasis, depending on the site of infection for particular species. These complexities threaten 350 million people in 98 countries worldwide. Amastigotes living within macrophage phagolysosomes are the principal target of antileishmanial treatment, but these are not an easy target as drugs must overcome major structural barriers. Furthermore, limitations on current therapy are related to efficacy, toxicity, and cost, as well as the length of treatment, which can increase parasitic resistance. Nanotechnology has emerged as an attractive alternative as conventional drugs delivered by nanosized carriers have improved bioavailability and reduced toxicity, together with other characteristics that help to relieve the burden of this disease. The significance of using colloidal carriers loaded with active agents derives from the physiological uptake route of intravenous administered nanosystems (the phagocyte system). Nanosystems are thus able to promote a high drug concentration in intracellular mononuclear phagocyte system (MPS)-infected cells. Moreover, the versatility of nanometric drug delivery systems for the deliberate transport of a range of molecules plays a pivotal role in the design of therapeutic strategies against leishmaniasis. This review discusses studies on nanocarriers that have greatly contributed to improving the efficacy of antileishmaniasis drugs, presenting a critical review and some suggestions for improving drug delivery.

Antimicrobial Activity of Lactoferrin-Related Peptides and Applications in Human and Veterinary Medicine.

Antimicrobial peptides (AMPs) represent a vast array of molecules produced by virtually all living organisms as natural barriers against infection. Among AMP sources, an interesting class regards the food-derived bioactive agents. The whey protein lactoferrin (Lf) is an iron-binding glycoprotein that plays a significant role in the innate immune system, and is considered as an important host defense molecule. In search for novel antimicrobial agents, Lf offers a new source with potential pharmaceutical applications. The Lf-derived peptides Lf(1-11), lactoferricin (Lfcin) and lactoferrampin exhibit interesting and more potent antimicrobial actions than intact protein. Particularly, Lfcin has demonstrated strong antibacterial, anti-fungal and antiparasitic activity with promising applications both in human and veterinary diseases (from ocular infections to osteo-articular, gastrointestinal and dermatological diseases).