Effect of surgery on oxidative stress and endogenous tocopherol concentrations in juvenile female dogs.

BACKGROUND: Surgery such as ovariectomy causes an inflammatory and oxidative stress. This study was designed to evaluate endogenous tocopherol levels in response to surgical oxidative stress induced by abdominal surgery (ovariectomy) in thirty-two juvenile female dogs. The dogs received meloxicam before surgery (0.2 mg/kg SC) and after surgery (0.1 mg/kg OS every 24 h), 0.03 mg/kg of atropine sulfate (IM), and propofol 4 mg/kg intravenously (IV). General anesthesia was maintained with sevoflurane. Physiological, hematological and biochemical parameters, malondialdehyde (MDA) and α-, δ-, γ-tocopherols were evaluated at baseline, 36 and 48 h after surgery. RESULTS: The physiological parameters remained within normal ranges. Blood glucose concentration increased, while the albumin levels decreased after surgery. Rescue analgesia was not required. MDA levels increased above the baseline at 36 and 48 h after surgery (P < 0.001). The α-, δ-, and γ-tocopherol concentrations decreased from baseline at 36 and 48 h after surgery (P < 0.001). CONCLUSIONS: Surgery in juvenile female dogs revealed oxidative, increased MDA concentrations, reduced tocopherol levels, and had a clinically insignificant influence on homeostasis.

Oxidative stress in relation to serotonin under general anaesthesia in dogs undergoing ovariectomy.

Abdominal surgery such as ovariectomy is a traumatic event that can cause oxidative stress. The aim of the present study was to evaluate the concentration of serotonin in relation to ovariectomy-induced oxidative stress in dogs undergoing general anesthesia. Thirty-two female dogs, under general anesthesia, received meloxicam before surgery (0.2 mgkg-1 SC) and after surgery (0.1 mgkg-1 OS every 24 h). The physiological, hematological, and biochemical parameters: glycemia, aspartate transaminase (AST), alanine aminotransferase (ALT), total protein, albumin and BUN were evaluated. Oxidative stress was determined by malondialdehyde (MDA) assay, catalase (CAT), superoxide dismutase (SOD), myeloperoxidase (MPO) and butyrylcholinesterase (BuChe) at baseline, 36 and 48 h after the last administration of meloxicam. Serotonin (5-HT) concentration was also evaluated at baseline, 36 and 48 h after the last administration of meloxicam. Responses to surgical stimulus were evaluated. Physiological and hematological parameters they fell within the normal ranges for anesthetized dogs. Glycemia increased, albumin levels decreased after surgery. No rescue analgesia was required. MDA and 5-HT concentrations significantly increased from the baseline at 36 and 48 h after surgery (p < .001). 5-HT levels could be used as an indicator for oxidative stress induced by surgery and it might be employed for objectively quantifying the well-being of the surgical patient.

Surgical Site Infiltration with Comfort-in Device and Traditional Syringe in Dogs Undergoing Regional Mastectomy: Evaluation of Intra- and Postoperative Pain and Oxidative Stress.

The surgical site infiltration of a local anesthetic is defined as the direct injection of a drug. This study aimed to compare the effects of surgical site infiltration with 4 mg kg-1 lidocaine using a Comfort-in device and traditional syringe on oxidative status and intra- and postoperative pain in dogs undergoing regional mastectomy. Sixty adult female dogs divided into C (Comfort-in device), S (traditional syringe), and CTR (control) groups received 2 µg kg-1 dexmedetomidine and 4 mg kg-1 tramadol IM, 5 mg kg-1 tiletamine/zolazepam IV, and isoflurane. The physiological and anesthesiological parameters were measured. The assessment of intra- and postoperative responses to the surgical stimulus was performed using a cumulative pain scale (CPS score of 0-4) and the Colorado Pain Scale (CSU-CAPS score of 0-4). The hematological and biochemical parameters and inflammatory oxidative status were measured. The CPS scores showed no significant differences between the C and S groups (p = 0.236), while the comparison between the CTR, C, and S groups, respectively, showed a significant difference (p < 0.001). The postoperative analgesia scores were significantly lower in the C group compared to those of the S and CTR groups (p < 0.001). In the C group, no subject received rescue analgesia during the intra- and postoperative periods. The level of oxidative inflammatory stress was lower in group C than those in S and CTR groups, and no side effects were observed in all the groups.

Occurrence and health risk assessment of mineral composition and aflatoxin M1 in cow milk samples from different areas of Sicily, Italy.

This study aimed to determine 16 mineral elements (Cd, Pb, As, Na, Mg, Al, Ca, K, Cr, Mn, Fe, Ni, Cu, Zn and Se) using inductively coupled plasma mass spectrometry (ICP-MS) and a direct mercury analyzer (DMA-80) for Hg evaluation. Aflatoxin M1 was determined by high-performance liquid chromatography with fluorescence detection (HPLC-FLD) in cow milk samples. This research considered 180 milk samples, 20 by province (Palermo, Catania, Messina), collected for a period of three years (2020-2022) to assess the potential risks for consumer, the safety status and nutritional quality related to mineral intake by consuming of milk. All samples showed a Pb concentration below the limit reported by European Regulation 915/2023. Cadmium and Hg concentrations were below the Limit Of Quantification (LOQ) in all samples analyzed. The milk samples analyzed proved to be a good source of Ca (up to 44.5 % of the dietary reference values), with well percentages also for Na (up to 7.6 %), K (up to 23.1 %) and Mg (up to 11.1 %). Regarding trace elements, the results reported that chromium requires attention; its value was always higher than 168.8 % in all samples analyzed. Levels of arsenic and lead were up to 20.2 % and up 7.1 % respectively. Aflatoxin M1 concentrations were below the limit of detection (< 0,009 mcg/kg) in all milk analyzed. Therefore, further studies are needed to safeguard consumer health, the quality of the product and to assess the state of animal health.

Intraoperative Isoflurane End-Tidal Concentration during Infusion of Fentanyl, Tramadol, or Fentanyl-Tramadol Combination in Cats.

The aim of this study was to evaluate the end-tidal concentration of isoflurane required, clinical parameters, intraoperative antinociceptive effect, and postoperative analgesia in cats undergoing ovariohysterectomy, receiving fentanyl, tramadol, or fentanyl/tramadol. Sixty-six cats in three groups, were premedicated with dexmedetomidine and infused with one of the following treatments: fentanyl, tramadol, or fentanyl/tramadol combination. Anesthesia was induced with alfaxolone and maintained with isoflurane, titrated to keep heart rate, respiratory rate and systolic arterial pressure within target values recorded at endotracheal intubation. An intraoperative cumulative scale was performed. Postoperatively, a short form of the Glasgow Composite Measure Pain Scale Feline was used at 2, 12, and 24 h. The groups were similar for age, weight, dose of dexmedetomidine, and alfaxalone administered. A greater reduction in the end-tidal isoflurane fraction was observed with the combined fentanyl/tramadol infusion than with either fentanyl or tramadol alone. No differences in the end-tidal isoflurane fraction were found between fentanyl or tramadol alone. Hemodynamic stability associated with minimal cardiopulmonary changes, low response to noxious intraoperative stimulation, and low postoperative pain scores were also observed with the fentanyl/tramadol combination. The fentanyl/tramadol combination provided a reduction in the end-tidal isoflurane fraction compared with fentanyl or tramadol alone.

Metal Content, Fatty Acid and Vitamins in Commercially Available Canned Fish on the Bulgarian Market: Benefit-Risk Ratio Intake.

Today, the distribution and consumption of canned products have become widespread due to the convenience of using processed fish products. This study aims to evaluate elements of toxicological concern and essential elements (Cd, Al, Cu, Cr, Mn, Fe, Pb, Ni, and Zn), the fatty acid composition, and the fat-soluble vitamin and antioxidant pigment contents of various canned fish products purchased on the Bulgarian market. The estimated weekly intake and human health benefit-risk ratio based on metal elements and n-3 LC-PUFA contents in canned fish products were assessed. The contents of the analyzed elements in the canned samples were found to be below the limits set by various health organizations. Al was detected in only one sample. The profile of fatty acids showed that the canned fish had high PUFA/SFA ratios, EPA + DHA contents and low SFA, AI and TI values. The analyzed canned fish contained significant contents of fat-soluble vitamins. The Atlantic bonito in a jar sample was characterized by a high percentage of vitamin A (26.7% RDI) and vitamin D3 (142% RDI) per 100 g portion. The calculated EWI value shows that the consumption of canned fish products did not present any risk. The benefit-risk ratio indicates that the canned fish species are safe for human consumption, except for one sample regarding Cr.

Heavy Metals Bioaccumulation in Mytilus galloprovincialis and Tapes decussatus from Faro Lake (Messina), Italy.

The aim of this study was to evaluate the potential bioaccumulation of arsenic (As), copper (Cu), zinc (Zn), cadmium (Cd), lead (Pb) and mercury (Hg) in the haemolymph and corpus of Mytilus galloprovincialis and Tapes decussatus from Lake Faro. The lake is particularly prone to the accumulation of substances that are potentially toxic to aquatic organisms, due to the input of pollutants from urban and agricultural sources and the low rate of water exchange. The combination of saltwater from the Tyrrhenian Sea, the Strait of Messina and freshwater from hilly aquifers has created brackish conditions in the lake, resulting in an area of high commercial shellfish productivity. As, Cd, Cu, Pb and Zn were determined using a single quadrupole inductively coupled plasma mass spectrometer; Hg was determined using a direct mercury analyser (DMA-80). Physicochemical parameters of the water from Lake Faro were also performed. Statistical analysis was carried out using GraphPad Prism 9.0 (GraphPad Software, Inc., Boston, MA, USA) and Shapiro-Wilk normality was applied. Concentrations of Cd, Hg and Pb below the permitted MRLs in Mytilus galloprovincialis and Tapes decussatus used as ''biological indicators'' show that Lake Faro is not at risk of contamination by these pollutants and, moreover, is free of health problems for the consumer based on regulatory limits.

Improved quality of life and pain relief in mature horses with osteoarthritis after oral transmucosal cannabidiol oil administration as part of an analgesic regimen.

The aim of this study was to evaluate the effect of oral cannabidiol (CBD) administration in addition to a conventional analgesic protocol on the clinical signs of 20 horses with mild joint osteoarthritis. The horses were randomly assigned to either the control group (C group) or the cannabidiol group (CBD group). Both groups were treated with phenylbutazone for 5 days. The CBD group received 0.03 mg/kg cannabidiol in hemp oil orally once daily for 14 days in addition to phenylbutazone treatment. All subjects were monitored for clinical parameters, oxidative status and blood counts. Pain and quality of life were also assessed using the Horse Chronic Pain Scale (HCPS). The CBD group showed a significant reduction in heart rate, respiratory rate, white blood cell count and oxidative stress (malondialdehyde lipid peroxidation). A significant reduction in HCPS scores was seen in both groups. Lower scores were recorded in the CBD group (3 med; range: 2/4) than in the C group (7 med; range: 4/10). The addition of a cannabidiol-based product to an analgesic protocol was well tolerated and showed positive effects on the treated subjects, improving their quality of life and pain relief.

Horse Whole Blood Trace Elements from Different Sicily Areas: Biomonitoring of Environmental Risk.

Horses are excellent bioindicators for the assessment of environmental pollution. The aim of this study was to evaluate the levels and potential bioaccumulation of 28 mineral elements in 75 horse whole blood samples collected from five pollution-prone areas of Sicily, Italy. A direct mercury analyzer (DMA-80) was used for Hg determination, and an inductively coupled plasma mass spectrometer (ICP-MS) for all other elements. A one-way ANOVA test, followed by Bonferroni's multiple comparison for post hoc comparison, was applied to assess statistically significant differences between mineral elements and the five experimental groups. The levels of mineral elements in hay and concentrate were below the limits set by Regulation No. 744/2012. The mineral content of whole blood samples was slightly influenced by the region of origin of the horse. p values < 0.05 were statistically meaningful. However, the concentrations of mineral elements in horses' whole blood remained within reference ranges. In conclusion, the present study shows that the mineral content does not represent a toxicological risk for the analyzed horses. In addition, the study areas did not appear to show a high mineral element contamination.

Tramadol vs. Lidocaine Administered Intraperitoneally and in Incisional Lines for the Intraoperative and Postoperative Pain Management of Romifidine-Telazol-Anesthetized Swine Undergoing Umbilical Hernia Repair.

The aim of the study was to compare the analgesic efficacy of tramadol and lidocaine for local anesthesia during umbilical hernia repair in swine. The study was performed on 66 large white crossbred swine. The swine received a mixture of tiletamine/zolazepam at 5 mg/kg and romifidine at 80 µg/kg, administered intramuscularly. Then, they were divided into three groups (n = 22) that received different treatments with lidocaine at 4 mg/kg and tramadol at 4 mg/kg. The LL group received lidocaine both by infiltration of the surgical planes and intraperitoneally. The LT group received lidocaine by infiltration of the surgical planes and tramadol intraperitoneally. The TT group received tramadol both by infiltration of the surgical planes and intraperitoneally. In all groups, the infiltration of the surgical planes into the umbilical region involved both the skin and muscle planes. Heart rate, noninvasive arterial blood pressure, and respiratory frequency were recorded during surgery. The response to the surgical stimulus was evaluated using a cumulative pain scale (the cut-off point for rescue analgesia was set to 10). Postoperative pain was assessed using the UNESP-Botucatu pig composite acute pain scale (the cut-off point was set to 4). The trend of physiological variables was adequate for patients under anesthesia. No subject required intraoperative and postoperative rescue analgesia. Tramadol could therefore be used for pain management in livestock.

Determination of Fatty Acid Profile in Processed Fish and Shellfish Foods.

Seafood products are a crucial dietary source of n-3 polyunsaturated fatty acids (n-3 PUFA), which are essential for human health. However, the presence of these n-3 PUFA may be subject to changes related to different processing methods. The aim of this study was to determine the fatty acid composition, focusing on n-3 PUFA, in different processed fish and shellfish products of both EU and non-EU origin. The products were purchased from supermarkets and ethnic food shops in Messina (Italy). Gas chromatography with a flame-ionization detector (GC-FID) was used for analysis. Based on the fatty acid profile, the atherogenicity index (AI), thrombogenicity index (TI), and flesh lipid quality index (FLQ) were determined: 0.13-1.04 (AI), 0.19-0.89 (TI), and 0.41-29.90 (FLQ). The percentages of saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids fell within the following ranges: 13.55-50.48%, 18.91-65.58%, and 13.84-52.73%, respectively. Considering that all samples showed low AI and TI indices and that all processed fish products proved to be a good source of beneficial PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), their consumption is recommended for humans.

Tramadol Administered Intravenously Either as a Bolus or a Slow Injection in Pain Management of Romifidine-Sedated Calves Undergoing Umbilical Hernia Repair.

Umbilical hernias in calves occur with relative frequency. Most abdominal surgeries can be performed in cattle using standing sedation and local blocks. Romifidine is widely used in calves, alone or in combination with opioids. Tramadol administered as an intravenous slow injection provided better analgesia than an IV bolus in cows. The aim of the present study was to compare the response to surgical stimulus, and sedative effects of tramadol administered intravenously either as a bolus or a slow injection in romifidinesedated calves. Twenty Frisian calves undergoing umbilical hernia repair received romifidine (0.08 mg/kg IM; time 0) followed by tramadol (1 mg/kg IV) 5 min later either as a bolus (n = 10, B group) or a slow injection over 10 min (n = 10, SI group). Surgical area was infiltrated with lidocaine (4 mg/kg). Heart rate (HR), respiratory rate (RR), systolic, dyastolic and mean arterial pressure (SAP, DAP, MAP), sedation scores and response to surgical stimulus were recorded for up to 55 min. After the calves recovered a standing position, postoperative pain scores were assessed for up to 50 min. Sedation scores were significantly higher in the SI group than in the B group at 55 min (p < 0.05). HR, RR, SAP and response to surgical stimulus were significantly higher in the B group than in the SI group (p < 0.05). No significant differences were recorded in postoperative pain scores between groups (p > 0.05). Romifidine IM followed by intravenous tramadol, as a bolus or slow injection and local infiltration with lidocaine provided adequate sedation and analgesia in calves undergoing umbilical hernia repair.

Seasonal Variations in the Trace Elements and Mineral Profiles of the Bivalve Species, Mytilus galloprovincialis, Chamelea gallina and Donax trunculus, and Human Health Risk Assessment.

This study aimed to provide data on selected toxic (Cd, Pb and Ni), essential (Cr, Cu, Fe, Mn and Zn) and microelement (Na, K, Ca and Mg) concentrations in edible tissues of the Mediterranean mussel (Mytilus galloprovincialis), striped venus clam (Chamelea gallina) and the wedge clam (Donax trunculus). Samples were collected from the Black Sea (Bulgaria) four times over, a period of one year (2022). In comparison with the maximum permissible levels set by the EU and USFDA, all elemental concentration found in the bivalve species were lower than the prescribed limits. An estimation of the dietary metal intake through calculation of the target hazard quotients (THQ), hazard index (HI) and target risk (TR) was performed. The target hazard quotient (THQ) for individual metal and HI for combined metals were lower than 1, indicating no health risk for consumers due to the intake of either individual element or combined ones. The target risk value for toxic inorganic Pb and Cr was below 10-6, indicating no carcinogenic risk. According to these results, the consumption of these bivalve species is completely safe for human health.

Snail Mucus Filtrate Reduces Inflammation in Canine Progenitor Epidermal Keratinocytes (CPEK).

Atopic dermatitis (AD) is an inflammatory and allergic disease, whose multifactorial etiopathogenesis is the consequence of the link between the genetic, immunological and environmental components. The complexity and difficulty in understanding the causes that trigger or exacerbate this pathology makes it difficult, once diagnosed, to proceed with a targeted and effective therapeutic process. Today, the new frontiers of research look to natural and innovative treatments to counteract the different manifestations of dermatitis. From this point of view, the mucus secreted by Helix aspersa Muller has proven, since ancient times, to be able to neutralize skin diseases. To study canine atopic dermatitis (cAD), we used cell lines of canine epidermal keratinocytes (CPEK) that are optimal to understand the biological reactivity of keratinocytes in vitro. The data obtained from our study demonstrate the anti-inflammatory capacity of snail secretion filtrate (SSF) in counteracting the production of proinflammatory cytokines produced during cAD, highlighting the opportunities for further studies to be able to identify new, natural and safe treatments for cAD and to open new frontiers for veterinarians and owners.

Mineral Composition in Delactosed Dairy Products: Quality and Safety Status.

Mineral elements are ingested through the diet (Li, Be, B, Na, Mg, Al, K, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Sr, Mo, Ag, Cd, Sb, Ba, Tl, Pb, and Bi). Essential minerals have structural, biochemical, nutritional and catalytic functions; therefore, they are fundamental for human health. In this research, thirty commercial delactosed dairy products from different varieties were supplied by various markets in Sicily (Italy), and their mineral contents were determined by using inductively coupled plasma mass spectrometry (ICP-MS) with the following aims: (1) to highlight the differences among various products; (2) to evaluate if it is possibly related to the analyzed samples of their product group; (3) to evaluate the nutritional quality and safety related to intake of these dairy products. Evident differences were found among the samples depending on the type of product. A good separation between mozzarella-on the one hand-and crescenza and primo sale-on the other-was observed. The mozzarella samples were distinguished by the higher Fe, V and Co contents, and the lower amount of Al. Based on shares of the RDA, the analyzed dairy samples are a good source of Ca (up to 58% of the nutrient reference values), with a relatively high concentration of Na (between 5.5% and 22%). Any safety risk for consumers due to exposures to toxic elements through analyzed samples is excluded. The obtained results give reason to expect further insight concerning the direct comparison between the delactosed and non-delactosed product, in order to evaluate if the manufacturing process can affect the content of some mineral.

Mineral content and physico-chemical parameters of honey from North regions of Algeria.

Honey is accepted as food and medicine by all generations both ancient and modern. In this study the concentrations of K, Mg, Na, Zn, Fe, Mn, Cu, Cr, Ni, Se, As, Pb, Cd, Sb, Ti, V, Co, Hg and the determination of some physico-chemical parameters in 29 multifloral honeys collected from different North regions of Algeria: Algiers, Bouria, Ghardaïa, Laghouat, M'sila, Naâma, Tlemcen and El Bayadth during year 2018 were carried out. All minerals were determined by ICP-OES/MS and Hg by DMA-80. The most abundant minerals decreased in the following order: K, Na, Mg, Fe, Zn. Lead content exceeded the Codex Alimentarius and the European Union in all honey samples analysed, Cd and As levels were lower than the limits fixed by the European legislation and the regulations of the Codex Alimentarius. The Recommended Dietary Allowance values and benchmark levels were employed to assess the honey quality and safety.

Data on multiple regression analysis between boron, nickel, arsenic, antimony, and biological substrates in horses: The role of hematological biomarkers.

The objective of this study was to evaluate the biomarkers of exposure to boron, nickel, arsenic, and antimony in an industrial region, evaluating the bioaccumulation in biological substrates and the correlation with biomarkers such as hematological parameters. Through indication of the accumulation of some minerals in the horse's biological substrates reflects environmental pollution. Moreover, an additional aim of the study was to show whether these contaminants have an influence on the hematological parameters in horses. Blood, serum, mane, and tail samples from 20 horses from an industrial area were analyzed to determine boron (B), nickel (Ni), arsenic (As), antimony (Sb) concentration. Hematological parameters (red blood cell [RBC], white blood cells [WBC], hemoglobin [Hb], hematocrit [Hct], mean corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], mean corpuscular hemoglobin concentration [MCHC], platelet [PLT]) as a biomarker of blood in relation to the bioaccumulation of these elements were analyzed also. Descriptive statistical analysis was performed and single regression analysis (Pearson) and multiple regression analysis (p < 0.05) between blood factors, As, B, Ni, and Sb concentrations, and for each mineral in different substrate, respectively. Results showed a significant correlation between tail and mane concentrations with serum and blood for boron concentration (r = -1 p < 0.05). No significant correlation between sample (feed, hay, mane, tail, and water) concentrations and As, Ni, and Sb were found. A significantly negative correlation with blood parameters (r = -1 p < 0.05) was observed in Boron concentration for mane and tail. This suggests that the mane and tail may be a potential means to investigate suspected exposure to excessive levels of trace minerals.

Effect of Cannabidiol (CBD) on Canine Inflammatory Response: An Ex Vivo Study on LPS Stimulated Whole Blood.

The use of cannabidiol (CBD) for animal species is an area of growing interest, for example for its anti-inflammatory and immuno-modulating properties, even though all of its biological effects are still not fully understood, especially in veterinary medicine. Therefore, the aim of this study was to investigate the anti-inflammatory and immuno-modulating properties of CBD for the first time directly in canine inflammatory response. We used an ex vivo model of LPS-stimulated whole dog blood. We stimulated the whole blood from healthy dogs with LPS 100 ng/mL for 24 h in the presence or not of CBD 50 and 100 µg/mL. We observed a reduction in IL-6 and TNF-α production from the group treated with CBD, but non-altered IL-10 levels. Moreover, we also observed from the CBD-treated group a reduction in Nf-κB and COX-2 expression. In conclusion, we demonstrated for the first time the anti-inflammatory and immuno-modulating properties of CBD directly in dogs' immune cells, using a canine ex vivo inflammatory model. The results obtained from these studies encourage further studies to better understand the possible therapeutic role of CBD in veterinary medicine.

The Protective Effect of Snail Secretion Filtrate in an Experimental Model of Excisional Wounds in Mice.

Wound healing is a physiological process comprising several coordinated phases, such as inflammation, proliferation, and remodeling. For centuries, Helix aspersa Muller mucus has been known to have biological properties that are useful for treating skin disorders. In this study, we used a full-thickness excisional wound model in mice to test the hypothesis that Snail Secretion Filtrate (SSF) can improve the wound healing process. The mucus from Helix aspersa Muller was obtained mechanically by manually stimulating snails with a sterile cotton swab tip, and then the mucus was subjected to a series of filtrations to obtain SSF. After wounding, the mice were treated topically with SSF for 14 days. Our macroscopic results show that the SSF treatment significantly improved the speed and percentage of wound area closure. Furthermore, SSF improved several markers of proper wound healing, such as collagen deposition (Masson, COL3A1, matrix metalloproteinases (MMPs)) and the tissue remodeling process (α-sma, vascular-endothelial growth factor (VEGF)). SSF was also able to counteract the inflammatory process in injured wound tissue (myeloperoxidase (MPO) IL-1ß, IL-6, TNF-α). In conclusion, our results show that SSF is able to enhance the speed and efficiency of wound healing and positively regulate several aspects of the wound healing process, such as the proliferative and remodeling phases.

D-Penicillamine: The State of the Art in Humans and in Dogs from a Pharmacological and Regulatory Perspective.

Chelant agents are the mainstay of treatment in copper-associated hepatitis in humans, where D-penicillamine is the chelant agent of first choice. In veterinary medicine, the use of D-penicillamine has increased with the recent recognition of copper-associated hepatopathies that occur in several breeds of dogs. Although the different regulatory authorities in the world (United States Food and Drugs Administration-U.S. FDA, European Medicines Agency-EMEA, etc.) do not approve D-penicillamine for use in dogs, it has been used to treat copper-associated hepatitis in dogs since the 1970s, and is prescribed legally by veterinarians as an extra-label drug to treat this disease and alleviate suffering. The present study aims to: (a) address the pharmacological features; (b) outline the clinical scenario underlying the increased interest in D-penicillamine by overviewing the evolution of its main therapeutic goals in humans and dogs; and finally, (c) provide a discussion on its use and prescription in veterinary medicine from a regulatory perspective.